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The concomitants of elevated erythrocyte sodium - lithium countertransport activity in diabetic nephropathy: a critical assessment

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Abstract

Elevated erythrocyte sodium-lithium countertransport activity is an intermediate phenotype of essential hypertension among Caucasians, and may also associate with kidney disease in type 1 (insulin-dependent) diabetes mellitus. Evidence supporting the hypothesis that an inherited predisposition to essential hypertension may thus partly identify with the genetic background of susceptibility to diabetic nephropathy is, however, controversial. This review discusses the possible points of controversy, with emphasis upon the need to standardize the manifest heterogeneity in the current techniques of measurement, as well as upon the clinical concomitants and interpretation of elevated sodium-lithium countertransport activity in type 1 diabetes mellitus. Large family studies may be required in order to single out the independent contributions of genes and environment to sodium-lithium countertransport activity in type 1 diabetes mellitus. However, the original hypothesis that genes underlying elevated sodium-lithium countertransport in essential hypertension and in diabetic nephropathy may also reflect in part a predisposition to diabetic kidney disease cannot be rejected on the basis of current evidence.

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References

  1. Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR, The changing natural history of nephropathy in type 1 diabetes. Am J Med 78:785–794, 1985

    Google Scholar 

  2. Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T, Diabetic nephropathy in type I (insulin-dependent) diabetes: an epidemiological study. Diabetologia 25:496–501, 1983

    Google Scholar 

  3. Seaqvist ER, Goetz FC, Rich S, Barbosa J, Familial clustering of diabetic kidney disease: evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 320:1161–1165, 1989

    Google Scholar 

  4. Viberti GC, Keen H, Wiseman MJ, Raised arterial pressure in parents of proteinuric insulin dependent diabetics. BMJ 295: 515–517, 1987

    Google Scholar 

  5. Krolewski AS, Canessa M, Warram JH, Laffel LMB, Christlieb AR, Knowler WC, Rand LI, Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus. N Engl J Med 318:140–145, 1988

    Google Scholar 

  6. Mangili R, Bending JJ, Scott G, Li LK, Gupta A, Viberti GC, Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy. N Engl J Med 318:146–150, 1988

    Google Scholar 

  7. Walker JD, Tariq T, Viberti GC, Sodium-lithium countertransport activity in red cells of patients with insulin dependent diabetes and nephropathy and their parents. BMJ 301:635–638, 1990

    Google Scholar 

  8. Jones SL, Trevisan R, Tariq T, Semplicini A, Mattrock M, Walker JD, Nosadini R, Viberti GC, Sodium-lithium countertransport in microalbuminuric insulin-dependent diabetic patients. Hypertension 15:570–575, 1990

    Google Scholar 

  9. Canessa M, Adragna N, Solomon HS, Connolly TM, Tosteson DC, Increased sodium-lithium countertransport in red cells of patients with essential hypertension. N Engl J Med 302:772–776, 1980

    Google Scholar 

  10. Turner ST, Weidman WH, Michels VV, Reed TJ, Ormson CL, Fuller T, Sing CF, Distribution of sodium-lithium countertransport and blood pressure in Caucasians five to eighty-nine years of age. Hypertension 13:378–391, 1989

    Google Scholar 

  11. Boerwinkle E, Turner ST, Weishilboum R, Johnson M, Richelson E, Sing CF, Analysis of the distribution of erythrocyte sodium-lithium countertransport in a sample representative of the general population. Genet Epidemiol 3:365–378, 1986

    Google Scholar 

  12. Hasstedt SJ, Wu LL, Ash KO, Kuida H, Williams RR, Hypertension and sodium-lithium countertransport in Utah pedigrees: evidence for major locus inheritance. Am J Hum Genet 43:14–22, 1988

    Google Scholar 

  13. Mangili R, Zerbini G, Garbetta F, Cusi D, Pastore MR, Bognetti E, Pozza G, Erythrocyte sodium-lithium countertransport and risk of nephropathy in type 1 (insulin-dependent) diabetes mellitus (abstract). Diabetologia 33:A12, 1990

  14. Zerbini G, Mangili R, Garbetta F, Cusi D, Barlassina C, Bianchi G, Pozza G, Erythrocyte sodium-lithium countertransport activity is elevated early in diabetic nephropathy (abstract) Diabetologia 33:A13, 1990

  15. Pezzali E, Mangili R, Garbetta F, Zerbini G, Secchi A, Spotti D, Pozza G, Parental cardiovascular disease and hypertension in type 1 (insulin-dependent) diabetic patients with nephropathy (abstract). Diabetologia 34 [Suppl 2]:A23, 1991

  16. Elving LD, Wetzels JFM, de Nobel E, Berden JHM, Erythrocyte sodium-lithium countertransport is not different in type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy. Diabetologia 34:126–128, 1991

    Google Scholar 

  17. Rutherford PA, Thomas TH, Carr SJ, Taylor R, Wilkinson R, Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy. Clin Sci 82:301–307, 1992

    Google Scholar 

  18. Jensen JS, Mathiesen ER, Nørgaard K, Hommel E, Borch-Johnson K, Funder J, Brahm J, Parving H-H, Deckert T, Increased blood pressure and erythrocyte sodium-lithium countertransport activity are not inherited in diabetic nephropathy. Diabetologia 33:619–624, 1992

    Google Scholar 

  19. Nosadini R, Fioretto P, Trevisan R, Crepaldi G, Insulin-dependent diabetes mellitus and hypertension. Diabetes Care 14: 210–219, 1991

    Google Scholar 

  20. Hilton PJ, Na+ transport in hypertension. Diabetes Care 14: 233–239, 1992

    Google Scholar 

  21. Huot SJ, Aronson PS, Na+−H+ exchanger and its role in essential hypertension and diabetes mellitus. Diabetes Care 14:521–535, 1991

    Google Scholar 

  22. Semplicini A, Mozzato MG, Samà B, Nosadini R, Fioretto P, Trevisan R, Pessina AC, Crepaldi G, Dal Palù C, Na/H and Li/Na exchange in red blood cells of normotensive and hypertensive patients with insulin dependent diabetes mellitus (IDDM). Am J Hypertens 2:174–177, 1989

    Google Scholar 

  23. Ibsen KK, Jensen HAE, Wieth JO, Funder J, Essential hypertension: sodium-lithium countertransport in erythrocytes from patients and from children having one hypertensive parent. Hypertension 4:703–709, 1982

    Google Scholar 

  24. Rutherford PA, Thomas TH, Carr SJ, Taylor R, Wilkinson R, Kinetics of sodium-lithium countertransport activity in patients with uncomplicated type I diabetes. Clin Sci 82:291–299, 1992

    Google Scholar 

  25. Rutherford PA, Thomas TH, Wilkinson R, Increased erythrocyte sodium-lithium countertransport activity in essential hypertension is due to an increased affinity for extracellular sodium. Clin Sci 79:365–369, 1990

    Google Scholar 

  26. Leatherbarrow RJ, Use of nonlinear regression to analyze enzyme kinetic data: application to situations of substrate contamination and background subtraction. Anal Biochem 177: 125–131, 1989

    Google Scholar 

  27. Cusi D, Barlassina C, Ferrandi M, Lupi P, Ferrari P, Bianchi G, Familial aggregation of cation transport abnormalities and essential hypertension. Clin Exp Hypertens 3:871–874, 1981

    Google Scholar 

  28. Hunt SC, Williams RR, Smith JB, Ash KO, Association of three erythrocyte cation transport systems with plasma lipids in Utah subjects. Hypertension 8:30–36, 1986

    Google Scholar 

  29. Williams RR, Hunt SC, Wu LL, Hasstedt SJ, Hopkins PN, Ash KO, Genetic and epidemiological studies on electrolyte transport systems in hypertension. Clin Physiol Biochem 6:136–149, 1988

    Google Scholar 

  30. Hunt SC, Hasstedt SJ, Kuida H, Stults BS, Hopkins BN, Williams RR, Genetic heritability and common environmental components of resting and stressed blood pressures, lipids and body mass index in Utah pedigrees and twins. Am J Epidemiol 129:625–638, 1989

    Google Scholar 

  31. Lifton RP, Hunt SC, Williams RR, Pouysségur J, Lalouel J-M, Exclusion of the Na-H antiporter as a candidate gene in human essential hypertension. Hypertension 17:8–14, 1991

    Google Scholar 

  32. Hunt SC, Williams RR, Ash KO, Changes in sodium-lithium countertransport correlate with changes in triglyceride levels and body mass index over 2 1/2 years of follow-up in Utah. Cardiovasc Drugs Ther 4 [Suppl 2]:357–362, 1990

    Google Scholar 

  33. Hunt SC, Stephenson SH, Hopkins PN, Hasstedt SJ, Williams RR, A prospective study of sodium-lithium countertransport and hypertension in Utah. Hypertension 17:1–7, 1991

    Google Scholar 

  34. Harris RC, Brenner BM, Seifter JL, Sodium-hydrogen exchange and glucose transport in renal microvillous membrane vesicles from rats with diabetes mellitus. J Clin Invest 77:724–733, 1986

    Google Scholar 

  35. Ng LL, Simmons D, Fright V, Garrido MC, Bomford J, Hockaday TDR, Leukocyte Na/H antiport activity in type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 33:371–377, 1990

    Google Scholar 

  36. Ng LL, Simmons D, Fright V, Garrido MC, Bomford J, Effect of protein kinase C modulators on the leukocyte Na/H antiport in type 1 (insulin-dependent) diabetic subjects with albuminuria. Diabetologia 33:278–284, 1990

    Google Scholar 

  37. Postnov YV, Kravtsov GM, Orlov SN, Pokudin NI, Postnov IY, Kotelevtsev YV, Effect of protein kinase C activation on cytoskeleton and cation transport in human erythrocytes. Hypertension 12:267–273, 1988

    Google Scholar 

  38. Semplicini A, Spalvins A, Canessa M, Kinetics and stoichiometry of the human red cell Na/H exchanger. J Membr Biol 107:219–228, 1989

    Google Scholar 

  39. Jain SK, McVie R, Duett J, Herbst JJ, Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes 38:1539–1543, 1989

    Google Scholar 

  40. Jain SK, Hyperglycaemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J Biol Chem 264:21340–21345, 1989

    Google Scholar 

  41. Jain SK, Levine SN, Duett J, Hollier B, Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats. Metabolism 39:971–975, 1990

    Google Scholar 

  42. Jensen T, Stender S, Deckert t, Abnormalities in plasma concentrations of lipoproteins and fibrinogen in type 1 (insulin-dependent) diabetic patients with increased urinary albumin excretion. Diabetologia 31:142–145, 1988

    Google Scholar 

  43. Jones SL, Close CF, Mattock MB, Jarrett RJ, Keen H, Viberti GC, Plasma lipid and coagulation factor concentrations in insulin-dependent diabetics with microalbuminuria. BMJ 298: 487–490, 1989

    Google Scholar 

  44. Laffel L, Warram JH, Krolewski AS, Increased blood pressure and erythrocyte sodium-lithium countertransport activity are not inherited in diabetic nephropathy (letter). Diabetologia 34: 452–454, 1991

    Google Scholar 

  45. Jensen JS, Borch-Johnsen K, Mathiesen ER, Funder J, Parving H-H, Deckert T, Nørgaard K, Increased blood pressure and erythrocyte sodium-lithium countertransport activity are not inherited in diabetic nephropathy (letter). Diabetologia 34: 453–454, 1991

    Google Scholar 

  46. Leslie RDG, Hardman T, Dubrey S, Lant AF, Increased lithium-sodium countertransport activity in identical twing discordant for type 1 diabetes (abstract). Diabetologia 34:A67, 1991.

  47. Carr S, Mbanya J-C, Thomas T, Keavey P, Taylor R, Alberti KGMM, Increase in glomerular filtration rate in patients with insulin-dependent diabetes and elevated erythrocyte sodium-lithium countertransport. N Engl J Med 322:500–504, 1990

    Google Scholar 

  48. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A, Albuminuria reflects widespread vascular damage: the steno hypothesis. Diabetologia 32:219–226, 1989

    Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Medicine, University of Milan, Scientific Institute San Raffaele, Milan, Italy

    R. Mangili & D. Gabellini

  2. Divisione Medicina I, Istituto Scientifico San Raffaele, Via Olgettina 60, I-20132, Milano, Italy

    G. Pozza

Authors
  1. R. Mangili
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  2. D. Gabellini
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  3. G. Pozza
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Mangili, R., Gabellini, D. & Pozza, G. The concomitants of elevated erythrocyte sodium - lithium countertransport activity in diabetic nephropathy: a critical assessment. Acta Diabetol 29, 221–226 (1992). https://doi.org/10.1007/BF00573492

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