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Post–renal transplantation hypophosphatemia
Post–Renal Transplantation Hypophosphatemia S. Seifi, M.L. Pezeshki, M.R. Khatami, M.M. Mazdeh, F. Ahmadi, and S. Maziar
H
YPOPHOSPHATEMIA is a common disorder following renal transplantation.1 Patients receiving a renal transplant from either a living related or a cadaveric donor, frequently (50%– 80%) develop hypophosphatemia.2 The decrease of serum inorganic phosphate concentration is associated with impaired renal tubular phosphate reabsorption and intestinal inorganic phosphate absorption.3 These patients often exhibit phosphaturia, decreased ratios of maximal rates of renal tubular transport of phosphate to glomerular filtration rates (TmPi/GFR), and increased rates of fractional excretion of Pi (FEpo4) in the presence of stable and normal glomerular filtration rates (GFRs).1,3 Renal proximal tubular phosphate reabsorption, which is a key component in overall Pi- homeostasis,4 is a Na⫹- dependent, secondary active process involving Na-Pi cotransport across the brush border membrane (BBM) as a rate-limiting step.3 Experimental data suggest that the type IIa renal apical BBM Na- Pi cotransporter mediates the majority of renal proximal tubule phosphate transport.1 Alterations in the activity or expression of this cotransporter account for physiological and pathophysiological changes in proximal tubular Pi reabsorption.4 Potential mediators of posttransplantation hypophosphatemia are increased PTH level and activity, relative deficiency of 1,25(OH)2D3, glucocorticoids, cyclosporine, phosphatonin, PHEX, or stanniocalcin.1 PTH has a phosphaturic effect. In some patients with posttransplantation hypophosphatemia, increased PTH levels and/or activity play a role in the decreased TmPi/GFR.5 1,25(OH)2D3 stimulates the BBM Na/Pi cotransporter in renal tubules and also in the upper small intestine.1 Although levels of 1,25(OH)2D3 usually revert to normal rapidly after successful renal transplantation,6 some patients still display relatively low levels of the active form of vitamin D3.1 Glucocorticoids decrease tubular reabsorption of phosphate by a direct and selective inhibitory effect on the Na/Pi cotransporters in renal and also intestinal BBM.6 In the presence of PHEX mutations, there may be increased levels of phosphatonin resulting in impaired renal proximal tubular Na/Pi cotransport7 and hypophosphatemia. The present study was designed to examine the incidence of post–renal transplantation hypophosphatemia and its correlation with transplanted kidney function.
METHODS This study serum includes the phosphate, Ca, Cr, and alkaline phosphatase values in 237 randomly selected patients who had undergone kidney transplantation. The examinations were performed 2 times per week for 8 weeks postoperatively. All data were analysed using SPSS.10 with comparisons of mean values between the 2 groups performed by paired t tests.
RESULTS
Among the 237 patients, 149 (63%) were men and 88 (37%) were women. Hypophosphatemia developed in 138 (58%) patients at a mean age of 38.4 years and a mean serum phosphate concentration of 1.83 ⫾ 0.34 mg/dL. None of the hypophosphatemic patients had a phosphate level ⬍1 mg/ dL; the minimum value was 1.1 mg/dL. The mean serum concentrations of creatinine, calcium, and alkaline phosphatase were 1.36 ⫾ 0.45 mg/dL, 9.1 mg/dL, and 210 U/L, respectively. Hypophosphatemia did not develop in 99 (42%) patients who had a mean age of 36 years and a mean serum creatinine concentration of 2.52 ⫾ 0.51 mg/dL. The difference between the mean serum creatinine values of hypophosphatemic and nonhypophosphatemic groups was statistically significant (P ⬍ .001). Therapy was started in all hypophosphatemic patients who displayed serum phosphate levels ⬍2.5 mg/dL. DISCUSSION
Patients who have undergone kidney transplantation manifest overt hypophosphatemia and also phosphaturia during the early period following transplantation, namely, 2 weeks to 1 month after surgery.3 The clinical significance of hypophosphatemia differs according to whether it occurs early or late after transplantation.8 During the first 4 months, many transplant recipients develop moderate hypophosphatemia, namely, serum phosphate concentrations between 0.9 and 2.25 mg/dL. A recent study observed 93% patients display this level.9 The main causes of increased urinary loss are primary allograft tubular dysfunction10 and persistent hyperparathyFrom the Department of Nephrology, Imam Khomeni Hospital, Tehran University of Medical Sciences, Tehran, Iran. Address reprint requests to S. Seifi, Department of Nephrology, Imam Khomeni Hospital, Tehran University of Medical Sciences, Keshavarz Blv., Tehran, Iran. E-mail: [email protected]
© 2003 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/03/$–see front matter doi:10.1016/j.transproceed.2003.08.056
Transplantation Proceedings, 35, 2645–2646 (2003)
2645
2646
roidism compounded by the effects of immunosuppressive and diuretic drugs.8 Severe phosphate depletion with serum phosphate concentrations ⬍0.9 mg/dL is rare, and may lead to hemolytic anemia, rhabdomyolysis, decreased myocardial contractility, and respiratory failure.8 Our study suggests that hypophosphatemia is a common disorder after renal transplantation (58% incidence), which is related to the functional performance of the transplanted kidney. REFERENCES 1. Levi M: Kidney Int 59:2377, 2001 2. Massari PU: Kidney Int 52:1412, 1997
SEIFI, PEZESHKI, KHATAMI ET AL 3. Green J, Debby H, Lederer E, et al: Kidney Int 60:1182, 2001 4. Murer H, Forster I, Hilfiker H, et al: Kidney Int 65(Suppl):S2, 1998 5. Steiner RW, Ziegler M, Halasz NA, et al: Transplantation 56:843, 1993 6. Loffing J, Lotscher M, Kaissling B, et al: J Am Soc Nephrol 9:1560, 1998 7. Drezner MK: Kidney Int 57:9, 2000 8. Torres A, Lorenzo V, Salido E, et al: J Am Soc Nephrol 13:551, 2002 9. Ambhul PM, Meier D, Wolf B, et al: Am J Kid Dis 34:875, 1999 10. Rosenbaum RW, Hruska KA, Korkor A, et al: Kidney Int 19:568, 1981
H
YPOPHOSPHATEMIA is a common disorder following renal transplantation.1 Patients receiving a renal transplant from either a living related or a cadaveric donor, frequently (50%– 80%) develop hypophosphatemia.2 The decrease of serum inorganic phosphate concentration is associated with impaired renal tubular phosphate reabsorption and intestinal inorganic phosphate absorption.3 These patients often exhibit phosphaturia, decreased ratios of maximal rates of renal tubular transport of phosphate to glomerular filtration rates (TmPi/GFR), and increased rates of fractional excretion of Pi (FEpo4) in the presence of stable and normal glomerular filtration rates (GFRs).1,3 Renal proximal tubular phosphate reabsorption, which is a key component in overall Pi- homeostasis,4 is a Na⫹- dependent, secondary active process involving Na-Pi cotransport across the brush border membrane (BBM) as a rate-limiting step.3 Experimental data suggest that the type IIa renal apical BBM Na- Pi cotransporter mediates the majority of renal proximal tubule phosphate transport.1 Alterations in the activity or expression of this cotransporter account for physiological and pathophysiological changes in proximal tubular Pi reabsorption.4 Potential mediators of posttransplantation hypophosphatemia are increased PTH level and activity, relative deficiency of 1,25(OH)2D3, glucocorticoids, cyclosporine, phosphatonin, PHEX, or stanniocalcin.1 PTH has a phosphaturic effect. In some patients with posttransplantation hypophosphatemia, increased PTH levels and/or activity play a role in the decreased TmPi/GFR.5 1,25(OH)2D3 stimulates the BBM Na/Pi cotransporter in renal tubules and also in the upper small intestine.1 Although levels of 1,25(OH)2D3 usually revert to normal rapidly after successful renal transplantation,6 some patients still display relatively low levels of the active form of vitamin D3.1 Glucocorticoids decrease tubular reabsorption of phosphate by a direct and selective inhibitory effect on the Na/Pi cotransporters in renal and also intestinal BBM.6 In the presence of PHEX mutations, there may be increased levels of phosphatonin resulting in impaired renal proximal tubular Na/Pi cotransport7 and hypophosphatemia. The present study was designed to examine the incidence of post–renal transplantation hypophosphatemia and its correlation with transplanted kidney function.
METHODS This study serum includes the phosphate, Ca, Cr, and alkaline phosphatase values in 237 randomly selected patients who had undergone kidney transplantation. The examinations were performed 2 times per week for 8 weeks postoperatively. All data were analysed using SPSS.10 with comparisons of mean values between the 2 groups performed by paired t tests.
RESULTS
Among the 237 patients, 149 (63%) were men and 88 (37%) were women. Hypophosphatemia developed in 138 (58%) patients at a mean age of 38.4 years and a mean serum phosphate concentration of 1.83 ⫾ 0.34 mg/dL. None of the hypophosphatemic patients had a phosphate level ⬍1 mg/ dL; the minimum value was 1.1 mg/dL. The mean serum concentrations of creatinine, calcium, and alkaline phosphatase were 1.36 ⫾ 0.45 mg/dL, 9.1 mg/dL, and 210 U/L, respectively. Hypophosphatemia did not develop in 99 (42%) patients who had a mean age of 36 years and a mean serum creatinine concentration of 2.52 ⫾ 0.51 mg/dL. The difference between the mean serum creatinine values of hypophosphatemic and nonhypophosphatemic groups was statistically significant (P ⬍ .001). Therapy was started in all hypophosphatemic patients who displayed serum phosphate levels ⬍2.5 mg/dL. DISCUSSION
Patients who have undergone kidney transplantation manifest overt hypophosphatemia and also phosphaturia during the early period following transplantation, namely, 2 weeks to 1 month after surgery.3 The clinical significance of hypophosphatemia differs according to whether it occurs early or late after transplantation.8 During the first 4 months, many transplant recipients develop moderate hypophosphatemia, namely, serum phosphate concentrations between 0.9 and 2.25 mg/dL. A recent study observed 93% patients display this level.9 The main causes of increased urinary loss are primary allograft tubular dysfunction10 and persistent hyperparathyFrom the Department of Nephrology, Imam Khomeni Hospital, Tehran University of Medical Sciences, Tehran, Iran. Address reprint requests to S. Seifi, Department of Nephrology, Imam Khomeni Hospital, Tehran University of Medical Sciences, Keshavarz Blv., Tehran, Iran. E-mail: [email protected]
© 2003 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/03/$–see front matter doi:10.1016/j.transproceed.2003.08.056
Transplantation Proceedings, 35, 2645–2646 (2003)
2645
2646
roidism compounded by the effects of immunosuppressive and diuretic drugs.8 Severe phosphate depletion with serum phosphate concentrations ⬍0.9 mg/dL is rare, and may lead to hemolytic anemia, rhabdomyolysis, decreased myocardial contractility, and respiratory failure.8 Our study suggests that hypophosphatemia is a common disorder after renal transplantation (58% incidence), which is related to the functional performance of the transplanted kidney. REFERENCES 1. Levi M: Kidney Int 59:2377, 2001 2. Massari PU: Kidney Int 52:1412, 1997
SEIFI, PEZESHKI, KHATAMI ET AL 3. Green J, Debby H, Lederer E, et al: Kidney Int 60:1182, 2001 4. Murer H, Forster I, Hilfiker H, et al: Kidney Int 65(Suppl):S2, 1998 5. Steiner RW, Ziegler M, Halasz NA, et al: Transplantation 56:843, 1993 6. Loffing J, Lotscher M, Kaissling B, et al: J Am Soc Nephrol 9:1560, 1998 7. Drezner MK: Kidney Int 57:9, 2000 8. Torres A, Lorenzo V, Salido E, et al: J Am Soc Nephrol 13:551, 2002 9. Ambhul PM, Meier D, Wolf B, et al: Am J Kid Dis 34:875, 1999 10. Rosenbaum RW, Hruska KA, Korkor A, et al: Kidney Int 19:568, 1981