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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 6  |  Page : 1154-1159
The effect of mannitol administration to kidney donor on short-term outcomes of kidney transplantation

Anesthesiology and Urology Department, Modaress Hospital, Shadi Beheshti University of Medical Science, Tehran, Iran

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Date of Web Publication10-Nov-2014


As the cases of kidney transplant are increasing, the need to apply the factors to increase the success of transplant seems necessary. Mannitol increases the osmotic pressure and urine volume as a protective agent on renal tubules. We aimed to evaluate the effect of mannitol on short-term outcome of kidney transplantation by comparing two groups based on prescribing mannitol to donors. In a randomized clinical trial, 60 kidney recipients were assigned in two groups (30 in each), except that in one group donors received mannitol. They were studied with respect to age, gender, weight, blood urea nitrogen (BUN), creatinine (Cr), sodium (Na), potassium (K) and arterial blood gas (ABG) before and after surgery, and their pulse rate (PR) and blood pressure (BP) before, during and after surgery. Their urine volume was assessed in the operation room and the first 24 h after surgery. The short-term outcome, including BUN and Cr in the first 10 days after transplant, have been charted. Both the case (mannitol-positive donor patient) and the control (mannitol negative) groups were the same regarding the results gained for pre- and post-operative parameters. Follow-up assessments showed no significant differences in renal function. Based on this, we conclude that mannitol administration to donors does not have a beneficial effect on the prognosis and short-term outcome of transplantation on recipients; therefore, we feel that it should not be advised for kidney donors.

How to cite this article:
Esfahani HS, Nooraei N, Asgary M, Hashemian MR. The effect of mannitol administration to kidney donor on short-term outcomes of kidney transplantation. Saudi J Kidney Dis Transpl 2014;25:1154-9

How to cite this URL:
Esfahani HS, Nooraei N, Asgary M, Hashemian MR. The effect of mannitol administration to kidney donor on short-term outcomes of kidney transplantation. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2020 May 31];25:1154-9. Available from: http://www.sjkdt.org/text.asp?2014/25/6/1154/144247

   Introduction Top

For patients with end-stage renal disease (ESRD), kidney transplantation is the most effective known treatment compared with hemodialysis and peritoneal dialysis. [1] Ischemia prevention in transplantation includes diuretics, Mannitol and dopamine; however, it is believed that mannitol as an osmotic diuretic has a better protective effect on renal tubules. [2],[3]

Although there are several studies on mannitol but no randomized clinical trials, this study was undertaken in the Modarres hospital to investigate the effect of mannitol on kidney transplantation and study the effectiveness of mannitol administration to kidney donors on the outcome of transplantation.

   Materials and Methods Top

This study was conducted as a randomized clinical trial from 20 September 2011 until 20 September 2012 in the urological operating room of the Modaress Hospital of Shahid Beheshti University of Medical Sciences, Tehran, Iran. Patients studied were those with diagnosed end-stage renal disease (ESRD) who underwent elective renal transplant.

After obtaining approval from the Central Ethics Committee of the Shahid Beheshti University, all patients were informed about the research process and informed written consent was obtained from them for the study. In this study, the healthy donors were divided into two groups of 30 each, one using and the other not using mannitol. In both the groups, gender and age were matched, with an age range of 18-55 years.

Exclusion criteria were: (1) all those who received organs from cadaver donors, (2) pa­tients with severe acid-base disorder (pH <7.15) and (3) all patients with significant and advanced cardiac disease (EF <20%).

Of the 60 selected patients, 30 persons were included in each group. Demographic and clin­ical data such as age, sex, weight, last dialysis time, BUN, Cr, Na, K, bicarbonate and vital signs were recorded on data collection forms. Then, randomization was performed with allo­cation of odd numbers to mannitol-positive do­nor patients and even numbers to mannitol-negative donor patients.

Patients were placed in one of the two groups according to the entry order. Patients were un­aware of their group, but the anesthesiologist in the operating room during surgery was aware of who received mannitol. However, the person who recorded the results was blinded about the groups of the patients.

Before surgery, venous catheters of guage 18 and 16 were placed to inject the fluids and medication to the patients. An arterial catheter of guage 20 was placed on the non-dominant hand after Allen's test and arterial samples during surgery were taken using this catheter. Before induction, arterial blood samples were taken for pH and blood gas analysis. Venous samples were sent for BUN, Cr and electrolytes.

Each patient was oxygenized with 100% oxy­gen for 3 min. For all patients, fentanyl 2 μg/kg and midazolam 0.03 mg/kg body weight were used. For induction, 4 mg/kg thiopental was used and as muscle relaxation for intubation, atracurium 0.5 mg/kg was given as a slow infu­sion. Anesthesia was maintained with isoflurane 0.6-1% followed by oxygen and N2O at 50% ratio. If necessary, during surgery, additio­nal doses of atracurium and fentanyl were used.

After induction, a central venous line via the right internal jugular vein was introduced. Intra­venous fluids 50 mL/kg to maintain the central vein pressure (CVP) about 10-12 cm of H 2 O was applied. During surgery, patients' temperature was kept constant at 36 degrees. Both groups were administrated intravenous Lasix in the same dose of 5 mg/kg and None of the patients required blood transfusion. For all donors, 50 mL/kg of normal saline was used. During the intraoperative period, arterial blood samples were taken every half hour to evaluate severe metabolic acidosis or hypokalemia in the reci­pients. Patients during hospitalization were followed-up closely and urine output as well as BUN and Cr values were measured and recor­ded daily on data collecting forms.

Information on quantitative variables between the case and control groups was recorded. Normality of variables was evaluated by the Kolmogorov-Smirnov test, box-whisker plot, normal probability and histogram. If the varia­bles were normal, the Student's t-test was used, else the Mann-Whitney test was applied. For comparison of variables measured at multiple times, repeated measured analysis was used. The effect of the case and control groups was examined and P-value was calculated. P <0.05 was considered to be significant. To compare the variables at two different times, due to the ab­sence of normal variables, the Wilcoxon test was applied.

   Results Top

All tests were two-tailed and conducted at the 5% significance level. Some of the data are as shown in the tables.

In terms of demographic variables, the diffe­rences of the two groups were not statistically significant. In addition, the two groups were stable with respect to hemodynamic variables during anesthesia and surgery. In case of pulse rate, the case and control groups were not significantly different (P = 0.31). Pre-operative BP readings between the groups were not sig­nificant (P = 0.233). The minimum BP measure­ment between the case and control groups remained nearly unchanged (P = 0.255).

The values of Na, K (before and after surgery), ABG, pH, HCO 3 , PCO 2 and urine volume in the operating room in the first 24 h did not show a significant difference between the two groups [Table 1].
Table 1: Comparison between the two groups in terms of Na, K, PH, HCO3 and PCO2 before and at the end of the operation.

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Urine volume in the operating room in the case group was 15588.36 ± 7453.7 and in the control group was 18758.00 ± 7612.1, with a P-value of 0.109 and urine volume at the first 24 h after surgery was 8575.86 ± 7282.05 in the study group and 9903.33 ± 8242.23 in the con­trol group, with a P-value of 0.285.

In repeated measurements in 10 consecutive days, the BUN difference between the two groups was not significant (P = 0.552) [Table 2]. On repeated measures analysis of Cr on 10 conse­cutive days, the difference between the two groups was not significant (P = 0.584) [Table 3].
Table 2: Comparison between two groups in terms of blood urea nitrogen (BUN) before anesthesia, after operation and the first 10 days after surgery.

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Table 3: Comparison between two groups in terms of creatinine before anesthesia, after operation and the first 10 days after surgery

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All of the kidney recipients had the same fluid therapy protocol in the kidney transplant ward after surgery as given below:

For the first 24 h, they take 100% urine out­put (normal saline/half saline/ringer) + 50 mL If BP <180/110: ringer/normal saline IfBP 180/110: half saline

For the next 24 h, they take 80% urine output oral intake (ringer/NS/Half saline) For the third 24 h, 3 L of ringer/NS/half saline From the fourth day, intravenous fluid adminisration was completely stopped.

   Discussion Top

We know that the kidney receives 25% of the cardiac output and, as an active mechanism, dilutes and reabsorbs the water. Ninety percent of oxygen uptake occurs in the renal medulla. Glomerular ultrafiltration depends on the ba­lance between afferent and efferent arterial tone. This was affected by the balance between vasodilators and vasoconstrictors.

Currently, mannitol is a protective factor in improving kidney function and, in many cen­ters, low-dose mannitol (0.25-0.5 mg/kg) is administrated to the recipients. Mannitol is an osmotic diuretic that increases renal blood flow (RBF) by releasing prostaglandin and atrial natriuretic peptide (ANP), causing intrarenal vasodilation and causes a decrease in renin production and endothelial cell swelling.

In Van Valenberg's study, it was demonstrated that mannitol is not effective without hydration. However, administration of 250 mL of 20% mannitol just before the release of renal artery clamp has been found to have a proven value if given after moderate hydration. [4]

According to the Lopez-Costeama study, adding mannitol to the perfusion solution decreases the ARF post-transplantation. [5] The study of Tiggeler showed that a moderate hydration regimen during operation with 2.5 L of fluids along with infusion of 250 mL of mannitol 20% just before clamp release will reduce the incidence of post-transplant acute tubular necrosis (ATN) to less than 5%. [6]

According to the study by Nissenson, mannitol acts as a diuretic by increasing urine volume and is important for the treatment of patients with edema and is also used in detoxification of toxins in patients treated with barbiturates, salicylate and bromide. [7]

Simon investigated the effects of hyperosmotic mannitol infusion on the hemodynamics of dog kidney and demonstrated that it increases ischemic blood flow by reducing intra-renal vascular resistance and increases glomerular filtration rate (GFR). [8]

A study by Reddy confirmed that increased volume alone is effective in acute renal failure (ARF), and that the presence of mannitol in just a sufficient volume reduces the incidence of ARF. [9]

In conformity with the Koning research on transplanted kidney, allograft factors conside­rably increased the incidence of delayed graft failure (DGF). The mean creatinine level (Cr >200 mm/L), prolonged cold ischemic time and previous transplant, non-intraoperative use of mannitol, poor quality of reperfusion, absence of intraoperative diuresis, pre-transplant anuria or oliguria were all found to be contributing factors. Therefore, the incidence of DGF can be reduced by the administration of mannitol during transplantation, which minimizes cool ischemic time and optimizes donor management. [10]

In a study by Gadallah, it was shown that a low dose of mannitol acts as a renal vasodila­tor while a high dose of mannitol is renal vaso­constrictor. Mannitol-induced ARF responds promptly to hemodialysis with rapid resolution of anuria and recovery of renal failure. [11]

In another study, in transplantations performed with short ischemia time and substantial vo­lume expansion combined with mannitol and furosemide administration, kidneys from living donors regained nearly normal function within a few hours after transplantation. [12]

The recent study of Hanif and colleagues showed variation in clinical practice on the use of intra-operative diuretics in renal transplan­tation, and it did not demonstrate that the use of diuretics can improve renal graft survival. The recipients were kept well hydrated with a combination of normal saline and 5% dextrose water to keep CVP 10-12 mm Hg during and after the transplants, especially in the imme­diate post-operative period. The study did not show any relation between the use of diuretics and improvement in renal graft survival. It has been well established that adequate hydration and stable blood pressure have a beneficial effect on the transplanted kidney, and the inci­dence of DGF and ATN can be reduced by these measures. [13]

Compared with the above, in our study, no significant difference has been observed. Based on this, we feel that mannitol administration to donors has no useful effect on the prognosis and short-term outcome of transplantation on recipients; therefore, should not be advised.

   Acknowledgment Top

The authors gratefully acknowledge the coope­ration of the staff, doctors and nurses in the operating room and kidney transplant depart­ment of the Shahid Moddares Hospital who has made this study a success.. Thanks are also due to the Shahid Beheshti University of Medical Science for the support received.

Conflict of interest: None

   References Top

Roberta L. Hines, Katherine E. Marschall. Renal diseases. In: Roberta L, Hines KE, eds. Marschall Stoelting's Anesthesia and Co-Existing disease, 5th ed. Philadelphia: Churchill Livingstone Elsevier; 2008. p. 384-5.  Back to cited text no. 1
C. Spencer Yost, Claus U. Niemann Anesthesia for Abdominal Organ Transplantation. In: Miller RD, ed. Miller's Anesthesia, 7th ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 2161-6.  Back to cited text no. 2
Malhotra V, Sudheendra V, O`Hara J, Diwan S. Anesthesia and the renal and Genitourinary Systems. In: Miller RD, ed. Miller's Anesthesia, 7th ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 2113-5.  Back to cited text no. 3
van Valenberg PL, Hoitsma AJ, Tiggeler RG, Berden JH, van Lier HJ, Koene RA. Mannitol as an indispensable constituent of an intraoperative hydration protocol for the prevention of acute renal failure after renal cadaveric transplantation. Transplantation 1987;44:784-8.  Back to cited text no. 4
Islam MK1, Rahman AT, Arif NU, et al. Modi­fied perfusion fluid for renal transplantation in developing countries: Our initial experience. Transplant Proc 2010;42:1531-5.  Back to cited text no. 5
Tiggeler RG, Berden JH. Hostma AJ, Koene RA. Prevention of acute tubular necrosis in cadaveric kidney transplantation by the com­bined use of mannitol and moderate hydration. Ann Surg 1985;201: 246-51.  Back to cited text no. 6
Nissenson AR, Weston RE, Kleeman CR. Mannitol. West J Med 1979;131:277-84.  Back to cited text no. 7
Gelman S. Does mannitol save the kidney? Anaesth Anlag 1996;82:899-901.  Back to cited text no. 8
Reddy VG. Prevention of postoperative acute renal failure. J Postgrad Med 2002;48:64-70.  Back to cited text no. 9
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Koning OH, Ploeg RJ, van Bckel JH, et al. Risk factors for delayed graft function in cadaveric kidney transplantation: A prospective study of renal function and graft survival after preser­vation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group. Transplantation 1997;63: 1620-8.  Back to cited text no. 10
Gadallah MF, Lynn M, Work J. Case report: Mannitol nephrotoxicity syndrome: Role of hemodialysis and postulate of mechanisms. Am J Med Sci 1995;309: 219-22.  Back to cited text no. 11
Bugge JF, Hartmann A, Osnes S, Bentdal O, Stenstrøm J. Immediate and early renal function after living donor transplantation. Nephrol Dial Transplant 1999;14:389-93.  Back to cited text no. 12
Hanif F, Macrae AN, Littlejohn MG, Clancy MJ, Murio E. Outcome of renal transplantation with and without intra-operative diuretics. Int J Surg 2011;9:460-3.  Back to cited text no. 13

Correspondence Address:
Dr. Hellieh Sadat Esfahani
Anesthesiology Department, Modaress Hospital, Shadi Beheshti University of Medical Science, Tehran
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DOI: 10.4103/1319-2442.144247

PMID: 25394430

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