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Mannitol infusion within 15 min of cross-clamp improves living donor kidney preservation.

Andrews PM, Cooper M, Verbesey J, Ghasemian S, Rogalsky D, Moody P, Chen A, Alexandrov P, Wang HW, Chen Y - Transplantation (2014)

Bottom Line: Specifically, we reduced the time of mannitol administration from 30 to 15 min or less before clamping the renal artery.OCT revealed that this change in the timing of mannitol administration protected the human donor proximal tubules from normothermic-induced cell swelling.An evaluation of posttransplant recovery of renal function showed that patients treated with this modified protocol returned to normal renal function significantly faster than those treated with mannitol 30 min or more before clamping the renal artery.

View Article: PubMed Central - PubMed

Affiliation: 1 Georgetown University Medical Center, Washington, DC. 2 Fischell Department of Bioengineering, University of Maryland, College Park, MD. 3 Address correspondence to: Peter M. Andrews, Ph.D., Georgetown University Medical Center, Washington, DC.

ABSTRACT

Background: Optical coherence tomography (OCT) revealed that cells lining proximal convoluted tubules of living donor kidneys (LDKs) procured by laparoscopic procedures were very swollen in response to the brief period of ischemia experienced between the time of arterial vessel clamping and flushing the excised kidney with cold preservation solution. Damage to the tubules as a result of this cell swelling resulted in varying degrees of acute tubular necrosis (ATN) that slowed the recovery of the donor kidneys during the first 2 weeks after their transplantation.

Methods: To prevent this cell damage during LDK procurement, we changed the protocol for intravenous administration of mannitol (i.e., 12.5 or 25 g) to the donor. Specifically, we reduced the time of mannitol administration from 30 to 15 min or less before clamping the renal artery.

Result: OCT revealed that this change in the timing of mannitol administration protected the human donor proximal tubules from normothermic-induced cell swelling. An evaluation of posttransplant recovery of renal function showed that patients treated with this modified protocol returned to normal renal function significantly faster than those treated with mannitol 30 min or more before clamping the renal artery.

Conclusion: Because slow graft recovery in the first weeks after transplantation represents a risk factor for long-term graft function and survival, we believe that this change in pretreatment protocol will improve renal transplants in patients receiving LDK.

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Related in: MedlinePlus

Graph comparing the mean posttransplant serum creatinine levels (±SEs) of individuals who received mannitol 15 min or less before clamping the renal artery (Group A, red ovals-red lines), with those of individuals who received mannitol 30 min or more before clamping the renal artery (Group B, black squares-black line). Individuals in Group A returned to within normal values (i.e., <1.4 mg/dL, indicated by dashed line) within 48 hours after transplant, whereas most in Group B remained elevated for 12 days after transplant.
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Figure 2: Graph comparing the mean posttransplant serum creatinine levels (±SEs) of individuals who received mannitol 15 min or less before clamping the renal artery (Group A, red ovals-red lines), with those of individuals who received mannitol 30 min or more before clamping the renal artery (Group B, black squares-black line). Individuals in Group A returned to within normal values (i.e., <1.4 mg/dL, indicated by dashed line) within 48 hours after transplant, whereas most in Group B remained elevated for 12 days after transplant.

Mentions: OCT imaging revealed a correlation between the presence of open proximal convoluted tubules in donor kidneys before transplantation, the timing of mannitol administration to the living donor, and posttransplant renal function. When the donor received mannitol (12.5–25 g iv,) 15 min or less before clamping the renal artery (i.e., Group A), the proximal convoluted tubules exhibited open lumens before transplant (Fig. 1A) with tubule diameters measuring ≈50 (±20) microns in diameter. The mean posttransplant renal function of individuals in Group A (i.e., 14 transplanted kidneys) was within the normal range (i.e., ≤1.4 mg/dL) within 2 days after transplant (Fig. 2). When, however, the donor received the same dose of mannitol 30 min or more before clamping the renal artery (i.e., Group B), cells lining the proximal convoluted tubules were swollen resulting in totally occluded tubule lumens immediately before their transplant (Fig. 1B). The appearance of the tubules was similar on both sides and both poles of the kidneys. Figure 1A and B are representative OCT images of the kidneys imaged in Groups A and B, respectively. The mean posttransplant renal function of individuals in Group B (i.e., 13 transplanted kidneys) did not return to within the normal range (i.e., ≤1.4 mg/dL) until 13 days after transplant (Fig. 2). The differences between patients in groups A versus B were significantly different on every day during the first week after transplant (i.e., P<0.05). Three-month data from the patients indicated a mean serum creatinine value of 1.13 mg/dL (± 0.06) for patients in Group A and versus 1.32 mg/dL (±0.11) for patients in Group B. Although the difference between the groups is not statistically different (i.e., P=0.16), five of the patients (i.e., 39%) in Groups B exhibited serum creatinine levels higher than normal (i.e., >1.4 mg/dL), whereas all the patients in Group A remained below 1.4 mg/dL at 3 months. Table 1 summarizes patient information for donors and recipients in Groups A and B. As noted in Table 1, the mean ages of the donors in both groups were nearly identical (i.e., 44.9 vs. 45.8 in Groups A and B, respectively), and the mean ages of the recipients were also nearly identical (i.e., 50.8 vs 51.4 in Groups A and B, respectively). Although the gender of the donors in Groups A versus B was similar, Group A had three more females receiving kidneys than Group B. The BMI (i.e., body mass indices) of patients in Groups B were higher than those in Group A (i.e., 24.5 vs. 29.4 for Groups A and B, respectively). Four patients in Group B were considered “obese” (i.e., BMI >30) versus only two in Group A. Nevertheless, only one of the patients in Group B that was categorized as “obese” was in the group with elevated serum creatinine values at the end of 3 months after transplantation. Therefore, obesity cannot be considered to be a significant factor affecting the long-term higher than normal serum creatinine levels of 4 of the 5 patients in Group B. No patients exhibited signs of rejection during the first 2 weeks after transplant. However, during the next two and a half months (i.e., up to 3 months after transplant), two patients in Group A exhibited signs of rejection that required additional therapy. There were no differences between Groups A versus B in the standard immunosuppression induction protocols after transplant that involved the use of alemtuzumab or basiliximab in combination with steroids.


Mannitol infusion within 15 min of cross-clamp improves living donor kidney preservation.

Andrews PM, Cooper M, Verbesey J, Ghasemian S, Rogalsky D, Moody P, Chen A, Alexandrov P, Wang HW, Chen Y - Transplantation (2014)

Graph comparing the mean posttransplant serum creatinine levels (±SEs) of individuals who received mannitol 15 min or less before clamping the renal artery (Group A, red ovals-red lines), with those of individuals who received mannitol 30 min or more before clamping the renal artery (Group B, black squares-black line). Individuals in Group A returned to within normal values (i.e., <1.4 mg/dL, indicated by dashed line) within 48 hours after transplant, whereas most in Group B remained elevated for 12 days after transplant.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 2: Graph comparing the mean posttransplant serum creatinine levels (±SEs) of individuals who received mannitol 15 min or less before clamping the renal artery (Group A, red ovals-red lines), with those of individuals who received mannitol 30 min or more before clamping the renal artery (Group B, black squares-black line). Individuals in Group A returned to within normal values (i.e., <1.4 mg/dL, indicated by dashed line) within 48 hours after transplant, whereas most in Group B remained elevated for 12 days after transplant.
Mentions: OCT imaging revealed a correlation between the presence of open proximal convoluted tubules in donor kidneys before transplantation, the timing of mannitol administration to the living donor, and posttransplant renal function. When the donor received mannitol (12.5–25 g iv,) 15 min or less before clamping the renal artery (i.e., Group A), the proximal convoluted tubules exhibited open lumens before transplant (Fig. 1A) with tubule diameters measuring ≈50 (±20) microns in diameter. The mean posttransplant renal function of individuals in Group A (i.e., 14 transplanted kidneys) was within the normal range (i.e., ≤1.4 mg/dL) within 2 days after transplant (Fig. 2). When, however, the donor received the same dose of mannitol 30 min or more before clamping the renal artery (i.e., Group B), cells lining the proximal convoluted tubules were swollen resulting in totally occluded tubule lumens immediately before their transplant (Fig. 1B). The appearance of the tubules was similar on both sides and both poles of the kidneys. Figure 1A and B are representative OCT images of the kidneys imaged in Groups A and B, respectively. The mean posttransplant renal function of individuals in Group B (i.e., 13 transplanted kidneys) did not return to within the normal range (i.e., ≤1.4 mg/dL) until 13 days after transplant (Fig. 2). The differences between patients in groups A versus B were significantly different on every day during the first week after transplant (i.e., P<0.05). Three-month data from the patients indicated a mean serum creatinine value of 1.13 mg/dL (± 0.06) for patients in Group A and versus 1.32 mg/dL (±0.11) for patients in Group B. Although the difference between the groups is not statistically different (i.e., P=0.16), five of the patients (i.e., 39%) in Groups B exhibited serum creatinine levels higher than normal (i.e., >1.4 mg/dL), whereas all the patients in Group A remained below 1.4 mg/dL at 3 months. Table 1 summarizes patient information for donors and recipients in Groups A and B. As noted in Table 1, the mean ages of the donors in both groups were nearly identical (i.e., 44.9 vs. 45.8 in Groups A and B, respectively), and the mean ages of the recipients were also nearly identical (i.e., 50.8 vs 51.4 in Groups A and B, respectively). Although the gender of the donors in Groups A versus B was similar, Group A had three more females receiving kidneys than Group B. The BMI (i.e., body mass indices) of patients in Groups B were higher than those in Group A (i.e., 24.5 vs. 29.4 for Groups A and B, respectively). Four patients in Group B were considered “obese” (i.e., BMI >30) versus only two in Group A. Nevertheless, only one of the patients in Group B that was categorized as “obese” was in the group with elevated serum creatinine values at the end of 3 months after transplantation. Therefore, obesity cannot be considered to be a significant factor affecting the long-term higher than normal serum creatinine levels of 4 of the 5 patients in Group B. No patients exhibited signs of rejection during the first 2 weeks after transplant. However, during the next two and a half months (i.e., up to 3 months after transplant), two patients in Group A exhibited signs of rejection that required additional therapy. There were no differences between Groups A versus B in the standard immunosuppression induction protocols after transplant that involved the use of alemtuzumab or basiliximab in combination with steroids.

Bottom Line: Specifically, we reduced the time of mannitol administration from 30 to 15 min or less before clamping the renal artery.OCT revealed that this change in the timing of mannitol administration protected the human donor proximal tubules from normothermic-induced cell swelling.An evaluation of posttransplant recovery of renal function showed that patients treated with this modified protocol returned to normal renal function significantly faster than those treated with mannitol 30 min or more before clamping the renal artery.

View Article: PubMed Central - PubMed

Affiliation: 1 Georgetown University Medical Center, Washington, DC. 2 Fischell Department of Bioengineering, University of Maryland, College Park, MD. 3 Address correspondence to: Peter M. Andrews, Ph.D., Georgetown University Medical Center, Washington, DC.

ABSTRACT

Background: Optical coherence tomography (OCT) revealed that cells lining proximal convoluted tubules of living donor kidneys (LDKs) procured by laparoscopic procedures were very swollen in response to the brief period of ischemia experienced between the time of arterial vessel clamping and flushing the excised kidney with cold preservation solution. Damage to the tubules as a result of this cell swelling resulted in varying degrees of acute tubular necrosis (ATN) that slowed the recovery of the donor kidneys during the first 2 weeks after their transplantation.

Methods: To prevent this cell damage during LDK procurement, we changed the protocol for intravenous administration of mannitol (i.e., 12.5 or 25 g) to the donor. Specifically, we reduced the time of mannitol administration from 30 to 15 min or less before clamping the renal artery.

Result: OCT revealed that this change in the timing of mannitol administration protected the human donor proximal tubules from normothermic-induced cell swelling. An evaluation of posttransplant recovery of renal function showed that patients treated with this modified protocol returned to normal renal function significantly faster than those treated with mannitol 30 min or more before clamping the renal artery.

Conclusion: Because slow graft recovery in the first weeks after transplantation represents a risk factor for long-term graft function and survival, we believe that this change in pretreatment protocol will improve renal transplants in patients receiving LDK.

Show MeSH
Related in: MedlinePlus