Skip to main content
NCBI home page
The BMJ logoLink to The BMJ
. 1990 Sep 29;301(6753):635–638. doi: 10.1136/bmj.301.6753.635

Sodium-lithium countertransport activity in red cells of patients with insulin dependent diabetes and nephropathy and their parents.

J D Walker 1, T Tariq 1, G Viberti 1
PMCID: PMC1663883  PMID: 2224216

Abstract

OBJECTIVE--To determine whether there are familial and genetic aspects of sodium-lithium countertransport activity in red cells in diabetic nephropathy. DESIGN--Case-control study. SETTING--Teaching hospital diabetic clinic. SUBJECTS--40 Patients with insulin dependent diabetes, both of whose parents were alive: 20 with persistent proteinuria and 20 with normal albumin excretion matched for age, duration of diabetes, and body mass index. All 80 parents. MAIN OUTCOME MEASURES--Sodium-lithium countertransport activity in red cells and arterial blood pressure. RESULTS--Sodium-lithium countertransport activity in red cells was higher in the patients with proteinuria than in the patients with normoalbuminuria (mean (95% confidence interval) 0.47 (0.39 to 0.54) v 0.33 (0.28 to 0.38) mmol/l red cells/h respectively, p = 0.0036; mean difference 0.14 (0.04 to 0.22)). The mean countertransport activity for the two parents of each patient was calculated, and from this the mean value for each group of parents was calculated; the value was higher in the parents of the patients with proteinuria than in the parents of the patients with normoalbuminuria (0.40 (0.32 to 0.48) v 0.30 (0.26 to 0.33) mmol/l red cells/h respectively, p = 0.016; 0.10 (0.02 to 0.19)). Twenty-eight of the parents of the patients with proteinuria compared with 12 of the parents of the patients with normoalbuminuria had a countertransport activity that was above the median value in all 80 parents (p less than 0.001). Mean arterial blood pressure in the parents of the patients with proteinuria was related to that of their offspring (r = 0.46; p less than 0.01). There was a positive correlation between the sodium-lithium countertransport activity in red cells in the parents and their offspring when all parents and patients were considered (r = 0.37; p less than 0.001). CONCLUSIONS--Increased sodium-lithium countertransport activity in red cells in the parents of diabetic patients with nephropathy provides further evidence that familial, and possibly genetic, factors related to a predisposition to arterial hypertension have a role in the susceptibility of diabetic renal disease.

Full text

PDF
635

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen A. R., Christiansen J. S., Andersen J. K., Kreiner S., Deckert T. Diabetic nephropathy in Type 1 (insulin-dependent) diabetes: an epidemiological study. Diabetologia. 1983 Dec;25(6):496–501. doi: 10.1007/BF00284458. [DOI] [PubMed] [Google Scholar]
  2. Boerwinkle E., Turner S. T., Weinshilboum R., Johnson M., Richelson E., Sing C. F. Analysis of the distribution of erythrocyte sodium lithium countertransport in a sample representative of the general population. Genet Epidemiol. 1986;3(5):365–378. doi: 10.1002/gepi.1370030509. [DOI] [PubMed] [Google Scholar]
  3. Canessa M. L., Morgan K., Semplicini A. Genetic differences in lithium-sodium exchange and regulation of the sodium-hydrogen exchanger in essential hypertension. J Cardiovasc Pharmacol. 1988;12 (Suppl 3):S92–S98. [PubMed] [Google Scholar]
  4. Canessa M., Adragna N., Solomon H. S., Connolly T. M., Tosteson D. C. Increased sodium-lithium countertransport in red cells of patients with essential hypertension. N Engl J Med. 1980 Apr 3;302(14):772–776. doi: 10.1056/NEJM198004033021403. [DOI] [PubMed] [Google Scholar]
  5. Canessa M., Bize I., Solomon H., Adragna N., Tosteson D. C., Dagher G., Garay R., Meyer P. Na countertransport and cotransport in human red cells: function, dysfunction, and genes in essential hypertension. Clin Exp Hypertens. 1981;3(4):783–795. doi: 10.3109/10641968109033702. [DOI] [PubMed] [Google Scholar]
  6. Carr S. J., Thomas T. H., Wilkinson R. Erythrocyte sodium-lithium countertransport in primary and renal hypertension: relation to family history. Eur J Clin Invest. 1989 Feb;19(1):101–106. doi: 10.1111/j.1365-2362.1989.tb00203.x. [DOI] [PubMed] [Google Scholar]
  7. Corrocher R., Steinmayr M., Ruzzenente O., Brugnara C., Bertinato L., Mazzi M., Furri C., Bonfanti F., De Sandre G. Elevation of red cell sodium-lithium countertransport in hyperlipidemias. Life Sci. 1985 Feb 18;36(7):649–655. doi: 10.1016/0024-3205(85)90169-9. [DOI] [PubMed] [Google Scholar]
  8. Deckert T., Poulsen J. E. Diabetic nephropathy: fault or destiny? Diabetologia. 1981 Sep;21(3):178–183. doi: 10.1007/BF00252651. [DOI] [PubMed] [Google Scholar]
  9. Hasstedt S. J., Wu L. L., Ash K. O., Kuida H., Williams R. R. Hypertension and sodium-lithium countertransport in Utah pedigrees: evidence for major-locus inheritance. Am J Hum Genet. 1988 Jul;43(1):14–22. [PMC free article] [PubMed] [Google Scholar]
  10. Hilton P. J. Cellular sodium transport in essential hypertension. N Engl J Med. 1986 Jan 23;314(4):222–229. doi: 10.1056/NEJM198601233140407. [DOI] [PubMed] [Google Scholar]
  11. Jones S. L., Trevisan R., Tariq T., Semplicini A., Mattock M., Walker J. D., Nosadini R., Viberti G. Sodium-lithium countertransport in microalbuminuric insulin-dependent diabetic patients. Hypertension. 1990 Jun;15(6 Pt 1):570–575. doi: 10.1161/01.hyp.15.6.570. [DOI] [PubMed] [Google Scholar]
  12. KEEN H., CHLOUVERAKIS C. AN IMMUNOASSAY METHOD FOR URINARY ALBUMIN AT LOW CONCENTRATIONS. Lancet. 1963 Nov 2;2(7314):913–914. doi: 10.1016/s0140-6736(63)90620-2. [DOI] [PubMed] [Google Scholar]
  13. Krolewski A. S., Canessa M., Warram J. H., Laffel L. M., Christlieb A. R., Knowler W. C., Rand L. I. Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus. N Engl J Med. 1988 Jan 21;318(3):140–145. doi: 10.1056/NEJM198801213180303. [DOI] [PubMed] [Google Scholar]
  14. Krolewski A. S., Warram J. H., Christlieb A. R., Busick E. J., Kahn C. R. The changing natural history of nephropathy in type I diabetes. Am J Med. 1985 May;78(5):785–794. doi: 10.1016/0002-9343(85)90284-0. [DOI] [PubMed] [Google Scholar]
  15. Mahnensmith R. L., Aronson P. S. The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. Circ Res. 1985 Jun;56(6):773–788. doi: 10.1161/01.res.56.6.773. [DOI] [PubMed] [Google Scholar]
  16. Mangili R., Bending J. J., Scott G., Li L. K., Gupta A., Viberti G. Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy. N Engl J Med. 1988 Jan 21;318(3):146–150. doi: 10.1056/NEJM198801213180304. [DOI] [PubMed] [Google Scholar]
  17. Morgan D. B., Stewart A. D., Davidson C. Relations between erythrocyte lithium efflux, blood pressure and family histories of hypertension and cardiovascular disease: studies in a factory workforce and hypertension clinic. J Hypertens. 1986 Oct;4(5):609–615. doi: 10.1097/00004872-198610000-00014. [DOI] [PubMed] [Google Scholar]
  18. Seaquist E. R., Goetz F. C., Rich S., Barbosa J. Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med. 1989 May 4;320(18):1161–1165. doi: 10.1056/NEJM198905043201801. [DOI] [PubMed] [Google Scholar]
  19. Semplicini A., Spalvins A., Canessa M. Kinetics and stoichiometry of the human red cell Na+/H+ exchanger. J Membr Biol. 1989 Mar;107(3):219–228. doi: 10.1007/BF01871937. [DOI] [PubMed] [Google Scholar]
  20. Smith J. B., Brock T. A. Analysis of angiotensin-stimulated sodium transport in cultured smooth muscle cells from rat aorta. J Cell Physiol. 1983 Mar;114(3):284–290. doi: 10.1002/jcp.1041140306. [DOI] [PubMed] [Google Scholar]
  21. Viberti G. C., Keen H., Wiseman M. J. Raised arterial pressure in parents of proteinuric insulin dependent diabetics. Br Med J (Clin Res Ed) 1987 Aug 29;295(6597):515–517. doi: 10.1136/bmj.295.6597.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Viberti G. C., Walker J. D. Diabetic nephropathy: etiology and prevention. Diabetes Metab Rev. 1988 Mar;4(2):147–162. doi: 10.1002/dmr.5610040205. [DOI] [PubMed] [Google Scholar]
  23. Watkins P. J., Blainey J. D., Brewer D. B., Fitzgerald M. G., Malins J. M., O'Sullivan D. J., Pinto J. A. The natural history of diabetic renal disease. A follow-up study of a series of renal biopsies. Q J Med. 1972 Oct;41(164):437–456. [PubMed] [Google Scholar]
  24. Weder A. B. Red-cell lithium-sodium countertransport and renal lithium clearance in hypertension. N Engl J Med. 1986 Jan 23;314(4):198–201. doi: 10.1056/NEJM198601233140402. [DOI] [PubMed] [Google Scholar]
  25. Williams R. R., Hunt S. C., Wu L. L., Hasstedt S. J., Hopkins P. N., Ash K. O. Genetic and epidemiological studies on electrolyte transport systems in hypertension. Clin Physiol Biochem. 1988;6(3-4):136–149. [PubMed] [Google Scholar]
  26. Worley R. J., Hentschel W. M., Cormier C., Nutting S., Pead G., Zelenkov K., Smith J. B., Ash K. O., Williams R. R. Increased sodium-lithium countertransport in erythrocytes of pregnant women. N Engl J Med. 1982 Aug 12;307(7):412–416. doi: 10.1056/NEJM198208123070706. [DOI] [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES