raffinose and Kidney-Diseases

Brain death is associated with hemodynamic disturbances in systemic circulation and metabolic storm, and, thus, free radical-mediated injury to donor tissues was hypothesized. An assessment of oxidative stress in the donor and its effect on posttransplant kidney graft function comprised the scope of the study.. A prospective study was performed in 27 donors and 50 kidney transplant recipients. Sera from 27 brain-dead organ donors and preservation media were tested for malondialdehyde (MDA) and for total antioxidant status (TAS). Kidneys were preserved in University of Wisconsin-gluconate solution with machine perfusion. Mean ischemia time was 36.7+/-8 hours. Organs were transplanted to recipients on the Polish National Waiting List and posttransplant kidney function was monitored periodically. Posttransplant delayed graft function (DF) was diagnosed when a patient required at least one dialysis within first week after transplantation. Acute rejection was diagnosed clinically and confirmed with fine-needle biopsy if necessary.. Thirty-two recipients had immediate graft function (IF), and 18 suffered from DF. MDA level in preservation solution at the end of machine perfusion was significantly higher in the DF group (52.6+/-31 vs. 25.3+/-19 micromol/L) whereas donor TAS activity was lower (1.14+/-0.2 vs. 0.97+/-0.3 mmol/mL). Patients who suffered from acute rejection received kidneys from donors with significantly higher serum MDA (66+/-73 micromol/ml vs. 23+/-49 for patients without rejection). Serum creatinine 12 to 48 months after transplantation correlated to donor- and preservation-solution MDA (P<0.006).. Free-radical mediated injury occurring in the donor and during preservation is strictly correlated with immediate and long-term kidney function. It may also cause grafts to be prone to acute rejection.

Topics: Acute Disease; Adenosine; Adolescent; Adult; Aged; Allopurinol; Antioxidants; Brain Death; Creatinine; Female; Free Radicals; Glutathione; Graft Rejection; Humans; Insulin; Kidney; Kidney Diseases; Kidney Transplantation; Male; Malondialdehyde; Middle Aged; Organ Preservation Solutions; Prognosis; Prospective Studies; Raffinose; Time Factors; Tissue Donors

Studies on kidney transplantation have thus far mainly dealt with surgical techniques, immunology, and transplant tolerance. Disturbed mineral metabolism after renal denervation has not received much attention. Basic physiological research in short-term experiments has shown that experimental renal denervation in rats leads to parathormone (PTH)-independent hyperphosphaturia (HPU). HPU and other metabolic complications also have been described after clinical kidney transplantation. Furthermore, there is an unexpected increase in the risk of bone fracture. However, these studies have examined an organism pre-damaged with regard to the parathyroid and immunosuppression. Experimental investigations in syngeneic rats were performed to see whether HPU also occurs after transplantation and thus after denervation and which target organs are involved.. Thirty-six male Lewis rats subjected to laparotomy (n = 12), unilateral nephrectomy (n = 12), or unilateral transplantation and bilateral nephrectomy (n = 12) were observed for 18 weeks.. Animals that underwent transplantation had a significant loss of phosphate in the urine not associated with decreased calcium, phosphate, or magnesium in bone. Stability test showed no deterioration, despite a slight increase in the bone parameters of alkaline phosphatase, cyclic AMP, and hydroxyproline with unchanged calciotropic hormones. Nephrocalcinosis was not observed. Parallel to HPU, there was a compensatory reduction in fecal phosphate excretion.. The loss of phosphate after clinical kidney transplantation in the predamaged parathyroid hormone control system as well as immunosuppression and a surprising increase in the incidence of bone fractures may be explained by the denervation-related loss of phosphate. The lack of intestinal counter-regulation could be an important pathomechanism.

Topics: Adenosine; Allopurinol; Animals; Bone and Bones; Calcinosis; Disease Models, Animal; Glutathione; Insulin; Kidney Diseases; Kidney Transplantation; Male; Nephrectomy; Organ Preservation; Organ Preservation Solutions; Phosphates; Raffinose; Rats; Rats, Inbred Lew; Tissue and Organ Harvesting; Transplantation, Isogeneic; Urinalysis

The present studies show clearly that both dexamethasone and insulin can be omitted without altering the efficacy of UW. Adenosine and glutathione are both helpful additives, as is allopurinol. These findings suggest an important role of reperfusion injury after preservation, and confirm the benefits of adding pharmacological agents likely to reduce this injury. Cold ischemic damage was significantly ameliorated by UW solution in this stringent model of rat kidney preservation for 48 hr. A substantially simplified modification of UW solution has been shown to give equally effective kidney preservation, after removal of hydroxyethyl starch, dexamethasone, and insulin. Adenosine, glutathione, and allopurinol have been confirmed as helpful pharmacological additives. These findings have defined some of the mechanisms of effectiveness of UW solution and suggest avenues of further exploration to improve simple hypothermic storage and to prevent reperfusion injury.

Topics: Adenosine; Allopurinol; Animals; Female; Glutathione; Insulin; Kidney Diseases; Kidney Transplantation; Male; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred Strains; Reperfusion Injury; Solutions; Tissue Preservation