Original article
Vol. 150 No. 4344 (2020)
Electrolyte disorders in stable renal allograft recipients
Summary
BACKGROUND
Acid base and electrolyte disorders are frequently reported in the early period after renal transplantation. No comprehensive data exist on the prevalence and patterns of, and contributing factors to, electrolyte disturbances in patients with stable long-term allograft function.
METHODS
We analysed 576 renal transplant recipients (serum creatinine level <2.0 mg/dl) in a cross-sectional study to evaluate the prevalence of electrolyte disorders and the risk factors associated with their occurrence.
RESULTS
A total of 369 patients (64%) of all allograft recipients (n = 576) showed at least one electrolyte and acid base disorder. The most abundant disorder was hypomagnesaemia (25%, n = 143), followed by hyperkalaemia (12.8%, n = 74), hypercalcaemia (12%, n = 69), hypophosphataemia (11.6%, n = 67), metabolic acidosis (11.1%, n = 61) and hyponatraemia (9%, n = 52). All other electrolyte disorders were rare (<6%). In most cases the electrolyte disorders could be classified as mild. Forty percent of the cases had a combined disorder, but without a preferential pattern of combinations. In a multivariate logistic regression analysis, the most important factors contributing significantly to the occurrence of electrolyte disorders were renal function and concomitant medications.
CONCLUSION
Acid base and electrolyte disorders are frequently observed in stable renal allograft recipients, but are usually mild. A combination of two or more electrolyte abnormalities often occurs, although no predominant pattern of a unique combination of electrolyte disorder is recognizable.
References
- Bricker NS, Guild WR, Merrill JP, Reardan JB. Studies on the functional capacity of a denervated homotransplanted kidney in an identical twin with parallel observations in the donor. J Clin Invest. 1956;35(12):1364–80.https://doi.org/10.1172/JCI103393
- Bricker NS, Straffon RA, Mahoney EP, Merrill JP. The functional capacity of the kidney denervated by autotransplantation in the dog. J Clin Invest. 1958;37(2):185–93.https://doi.org/10.1172/JCI103597
- Coruzzi P, Musiari L, Mossini GL, Ceriati R, Mutti A. The renin-aldosterone system and renal function in kidney transplantation. Clin Nephrol. 1994;41(4):225–9.
- Blaufox MD, Lewis EJ, Jagger P, Lauler D, Hickler R, Merrill JP. Physiologic responses of the transplanted human kidney. N Engl J Med. 1969;280(2):62–6.https://doi.org/10.1056/NEJM196901092800202
- Heering P, Degenhardt S, Grabensee B. Tubular dysfunction following kidney transplantation. Nephron. 1996;74(3):501–11.https://doi.org/10.1159/000189443
- Velic A, Hirsch JR, Bartel J, Thomas R, Schröter R, Stegemann H, et al. Renal transplantation modulates expression and function of receptors and transporters of rat proximal tubules. J Am Soc Nephrol. 2004;15(4):967–77.https://doi.org/10.1097/01.ASN.0000117287.74203.89
- Pochineni V, Rondon-Berrios H. Electrolyte and Acid-Base Disorders in the Renal Transplant Recipient. Front Med (Lausanne). 2018;5:261.https://doi.org/10.3389/fmed.2018.00261
- Mitterbauer C, Heinze G, Kainz A, Kramar R, Hörl WH, Oberbauer R. ACE-inhibitor or AT2-antagonist therapy of renal transplant recipients is associated with an increase in serum potassium concentrations. Nephrol Dial Transplant. 2008;23(5):1742–6.https://doi.org/10.1093/ndt/gfm864
- Schwarz C, Benesch T, Kodras K, Oberbauer R, Haas M. Complete renal tubular acidosis late after kidney transplantation. Nephrol Dial Transplant. 2006;21(9):2615–20.https://doi.org/10.1093/ndt/gfl211
- Gettes LS. Electrolyte abnormalities underlying lethal and ventricular arrhythmias. Circulation. 1992;85(1, Suppl):I70–6.
- Jeon HJ, Kim YC, Park S, Kim CT, Ha J, Han DJ, et al. Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2017;12(4):653–62.https://doi.org/10.2215/CJN.07090716
- Han SS, Han M, Park JY, An JN, Park S, Park S-K, et al. Posttransplant Hyponatremia Predicts Graft Failure and Mortality in Kidney Transplantation Recipients: A Multicenter Cohort Study in Korea. PLoS One. 2016;11(5):e0156050.https://doi.org/10.1371/journal.pone.0156050
- Park S, Kang E, Park S, Kim YC, Han SS, Ha J, et al. Metabolic Acidosis and Long-Term Clinical Outcomes in Kidney Transplant Recipients. J Am Soc Nephrol. 2017;28(6):1886–97.https://doi.org/10.1681/ASN.2016070793
- Lindner G, Schwarz C. Electrolyte-free water clearance versus modified electrolyte-free water clearance: do the results justify the effort? Nephron, Physiol. 2012;120(1):1–5.https://doi.org/10.1159/000336550
- Payne RB. Renal tubular reabsorption of phosphate (TmP/GFR): indications and interpretation. Ann Clin Biochem. 1998;35(2):201–6.https://doi.org/10.1177/000456329803500203
- Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration. Lancet. 1975;306(7929):309–10.https://doi.org/10.1016/S0140-6736(75)92736-1
- Smalcelj R, Kusec V. Gestörte Regulation der Calcium Ausscheidung bei Nierentransplantierten [Impaired regulation of calcium excretion in kidney transplant recipients]. Wien Klin Wochenschr. 2011;123(11-12):334–9.https://doi.org/10.1007/s00508-011-1575-6
- Masson I, Flamant M, Maillard N, Rule AD, Vrtovsnik F, Peraldi M-N, et al. MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients. Transplantation. 2013;95(10):1211–7.https://doi.org/10.1097/TP.0b013e318288caa6
- Havlin J, Matousovic K, Schück O. Sodium-Chloride Difference as a Simple Parameter for Acid-Base Status Assessment. Am J Kidney Dis. 2017;69(5):707–8.https://doi.org/10.1053/j.ajkd.2016.12.019
- von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP ; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4(10):e296.https://doi.org/10.1371/journal.pmed.0040296
- Higgins R, Ramaiyan K, Dasgupta T, Kanji H, Fletcher S, Lam F, et al. Hyponatraemia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities. Nephrol Dial Transplant. 2004;19(2):444–50.https://doi.org/10.1093/ndt/gfg515
- Van de Cauter J, Sennesael J, Haentjens P. Long-term evolution of the mineral metabolism after renal transplantation: a prospective, single-center cohort study. Transplant Proc. 2011;43(9):3470–5.https://doi.org/10.1016/j.transproceed.2011.09.030
- Van Laecke S, Van Biesen W. Hypomagnesaemia in kidney transplantation. Transplant Rev (Orlando). 2015;29(3):154–60.https://doi.org/10.1016/j.trre.2015.05.002
- Boonpheng B, Thongprayoon C, Bathini T, Sharma K, Mao MA, Cheungpasitporn W. Proton pump inhibitors and adverse effects in kidney transplant recipients: A meta-analysis. World J Transplant. 2019;9(2):35–47.https://doi.org/10.5500/wjt.v9.i2.35
- Douwes RM, Gomes-Neto AW, Schutten JC, van den Berg E, de Borst MH, Berger SP, et al. Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients. J Clin Med. 2019;8(12):2162.https://doi.org/10.3390/jcm8122162
- Nijenhuis T, Hoenderop JGJ, Bindels RJM. Downregulation of Ca(2+) and Mg(2+) transport proteins in the kidney explains tacrolimus (FK506)-induced hypercalciuria and hypomagnesemia. J Am Soc Nephrol. 2004;15(3):549–57.https://doi.org/10.1097/01.ASN.0000113318.56023.B6
- Palmer SC, Mavridis D, Navarese E, Craig JC, Tonelli M, Salanti G, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet. 2015;385(9982):2047–56.https://doi.org/10.1016/S0140-6736(14)62459-4
- Evenepoel P, Claes K, Kuypers D, Maes B, Bammens B, Vanrenterghem Y. Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study. Nephrol Dial Transplant. 2004;19(5):1281–7.https://doi.org/10.1093/ndt/gfh128
- Evenepoel P, Van Den Bergh B, Naesens M, De Jonge H, Bammens B, Claes K, et al. Calcium metabolism in the early posttransplantation period. Clin J Am Soc Nephrol. 2009;4(3):665–72.https://doi.org/10.2215/CJN.03920808
- Wolf M, Weir MR, Kopyt N, Mannon RB, Von Visger J, Deng H, et al. A Prospective Cohort Study of Mineral Metabolism After Kidney Transplantation. Transplantation. 2016;100(1):184–93.https://doi.org/10.1097/TP.0000000000000823
- Messa P, Cafforio C, Alfieri C. Clinical impact of hypercalcemia in kidney transplant. Int J Nephrol. 2011;2011:906832.https://doi.org/10.4061/2011/906832
- Reinhardt W, Bartelworth H, Jockenhövel F, Schmidt-Gayk H, Witzke O, Wagner K, et al. Sequential changes of biochemical bone parameters after kidney transplantation. Nephrol Dial Transplant. 1998;13(2):436–42.https://doi.org/10.1093/oxfordjournals.ndt.a027843
- Borchhardt K, Sulzbacher I, Benesch T, Födinger M, Sunder-Plassmann G, Haas M. Low-turnover bone disease in hypercalcemic hyperparathyroidism after kidney transplantation. Am J Transplant. 2007;7(11):2515–21.https://doi.org/10.1111/j.1600-6143.2007.01950.x
- Khosroshahi HT, Shoja MM, Azar SA, Tubbs RS, Safa J, Etemadi J, et al. Calcium and phosphorus metabolism in stable renal transplant recipients. Exp Clin Transplant. 2007;5(2):670–2.
- Evenepoel P, Meijers BKI, de Jonge H, Naesens M, Bammens B, Claes K, et al. Recovery of hyperphosphatoninism and renal phosphorus wasting one year after successful renal transplantation. Clin J Am Soc Nephrol. 2008;3(6):1829–36.https://doi.org/10.2215/CJN.01310308
- Glatz N, Chappuis A, Conen D, Erne P, Péchère-Bertschi A, Guessous I, et al. Associations of sodium, potassium and protein intake with blood pressure and hypertension in Switzerland. Swiss Med Wkly. 2017;147:w14411.
- Hoorn EJ, Walsh SB, McCormick JA, Fürstenberg A, Yang C-L, Roeschel T, et al. The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension. Nat Med. 2011;17(10):1304–9.https://doi.org/10.1038/nm.2497
- van der Wijst J, Tutakhel OAZ, Bos C, Danser AHJ, Hoorn EJ, Hoenderop JGJ, et al. Effects of a high-sodium/low-potassium diet on renal calcium, magnesium, and phosphate handling. Am J Physiol Renal Physiol. 2018;315(1):F110–22.https://doi.org/10.1152/ajprenal.00379.2017
- Bantle JP, Nath KA, Sutherland DE, Najarian JS, Ferris TF. Effects of cyclosporine on the renin-angiotensin-aldosterone system and potassium excretion in renal transplant recipients. Arch Intern Med. 1985;145(3):505–8.https://doi.org/10.1001/archinte.1985.00360030153026
- Foley RJ, Hamner RW, Weinman EJ. Serum potassium concentrations in cyclosporine- and azathioprine-treated renal transplant patients. Nephron. 1985;40(3):280–5.https://doi.org/10.1159/000183479
- Heering PJ, Kurschat C, Vo DT, Klein-Vehne N, Fehsel K, Ivens K. Aldosterone resistance in kidney transplantation is in part induced by a down-regulation of mineralocorticoid receptor expression. Clin Transplant. 2004;18(2):186–92.https://doi.org/10.1046/j.1399-0012.2003.00154.x
- Aguilera S, Deray G, Desjobert H, Benhmida M, Le Hoang P, Jacobs C. Effects of cyclosporine on tubular acidification function in patients with idiopathic uveitis. Am J Nephrol. 1992;12(6):425–30.https://doi.org/10.1159/000168493
- Musso CG, Castañeda A, Giordani M, Mombelli C, Groppa S, Imperiali N, et al. Hyponatremia in kidney transplant patients: its pathophysiologic mechanisms. Clin Kidney J. 2018;11(4):581–5.https://doi.org/10.1093/ckj/sfy016
- Morales JM, Wramner L, Kreis H, Durand D, Campistol JM, Andres A, et al.; Sirolimus European Renal Transplant Study Group. Sirolimus does not exhibit nephrotoxicity compared to cyclosporine in renal transplant recipients. Am J Transplant. 2002;2(5):436–42.https://doi.org/10.1034/j.1600-6143.2002.20507.x
- Schwarz C, Böhmig GA, Steininger R, Mayer G, Oberbauer R. Impaired phosphate handling of renal allografts is aggravated under rapamycin-based immunosuppression. Nephrol Dial Transplant. 2001;16(2):378–82.https://doi.org/10.1093/ndt/16.2.378
- Kamińska J, Sobiak J, Suliburska JM, Duda G, Głyda M, Krejpcio Z, et al. Effect of mycophenolate mofetil on plasma bioelements in renal transplant recipients. Biol Trace Elem Res. 2012;145(2):136–43.https://doi.org/10.1007/s12011-011-9178-7