Donor age and graft function

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7-16) years in 46 patients [median age 11.8 years (range) 3-16.8 years]. The median age of the adult donors was 34.4 (19-54) years in 59 patients [median age 12.1 years (range) 7-17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of 51chromium-EDTA and 125iodine-hippurate 1-48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2-3 months after transplantation the GFR in recipients of pediatric grafts was 62 +/- 20 ml/min per 1.73 m2 compared with 61 +/- 21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486 +/- 239 versus 362 +/- 158 ml/min per 1.73 m2. From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279 +/- 131 ml/min per 1.73 m2 compared with 273 +/- 123 ml/min per 1.73 m2 in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2-3 months after transplant the mean GFR of grafts from pediatric donors increased to 118% +/- 51%, whereas the GFR of adult donor grafts fell to 60% +/- 22% over the same period. After 4-6 months the ERPF in pediatric grafts was 96% +/- 55% compared with 50% +/- 22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient.     

Renal reserve is normal in adults born with unilateral renal agenesis and is not related to hyperfiltration or renal failure

This study was carried out to examine the renal hemodynamic response in adult patients with single kidneys born with unilateral renal agenesis. A group of 21 patients with unilateral renal agenesis were divided into three groups according to their glomerular filtration rate (GFR): 112 +/- 3 ml/min x 1.73 m2 in group A, 68 +/- 3.2 ml/min x 1.73 m2 in group B, and 40.7 +/- 3.3 ml/min x 1.73 m2 in group C. Mean arterial blood pressure was significantly higher in the patients of group C who were also proteinuric. The renal hemodynamic response to an oral protein load (2 g/kg of protein as beefsteak) was normal in all groups and unrelated to hyperfiltration or to renal failure and proteinuria. The study indicates that in patients with renal agenesis, the hemodynamic response to a protein challenge is similar to that of kidney donors, renal transplant recipients and uninephrectomized patients. The paper also demonstrates that the renal response to a protein challenge is inadequate to identify patients with renal agenesis who are at risk of developing renal disease. Finally, in renal agenesis with renal disease, creatinine clearance overestimated the GFR by an average of 32.7%.     

Role of the donor in post-transplant renal function

BACKGROUND: The donor, i.e. adult or paediatric, might influence the outcome of the graft function. METHODS: The glomerular filtration rate (GFR) of 120 transplanted children (47 girls) aged 10.4+/-4.6 years (0.7-17.2) was prospectively assessed over a 5-year period. The patients were divided into two groups according to the age of donor: adult (donor age > 18 years; n=33) and paediatric (donor age < 18 years; n=87). GFR was assessed by inulin clearance at 3, 6 and 12 months and yearly thereafter. RESULTS: The average GFR was stable in the range of 70 ml/min/1.73 m2 for the whole follow-up period. The adjusted GFR in adult graft recipients was significantly higher at 3 months post-transplantation: 80.6+/-36.9 vs 65.1+/-22.0, P=0.02. However, from the second year post-transplantation, the adjusted GFR in paediatric graft recipients became significantly higher than that of adult graft recipients. Such results could be due to an improvement in the absolute GFR (ml/min) of paediatric graft recipients with time (P=0.0001) whereas that of the adult graft recipients remained stable despite the children's growth. CONCLUSIONS: The adjusted GFR of adult graft recipients was significantly higher than that of paediatric graft recipients in the early post-transplant period. In the long-term, a progressive decrease in adjusted GFR was noted in adult graft recipients. On the one hand, this may be due to a functional adaptation and/or inadequate compensatory growth of the graft. On the other hand, the absolute GFR of paediatric graft recipients increased, suggesting an ongoing capacity for growth and/or compensatory hypertrophy after child-to-child renal transplantation.     

Renal excretion of sodium in individuals with stabilized renal graft function

In subjects with a transplanted kidney frequently tubular functions are impaired even when the glomerular filtration is within the normal range. In the present work the authors are dealing in more detail with the problem of tubular sodium reabsorption in the transplanted kidney. The purpose of the investigation was to assess to what extent these changes can be explained as the consequence of adaptational changes due to reduction of the number of nephrons and whether these changes have to be taken into consideration in the differential diagnosis of acute changes of graft function. The glomerular filtration rate (GF) was assessed on the basis of polyfructosan clearance, fractional sodium and potassium excretion (FENa and FEK) in a group of 12 subjects with a stabilized function of a transplanted kidney (group A), in 11 subjects after nephrectomy in healthy donors for transplantation (group B) and in 27 subjects after nephrectomy indicated for a pathological process in one kidney (group C). The mean values of GFR were as follows: Group A: 1.21 (+/- 0.19)ml/s/1.73 sq.m Group B: 1.19 (+/- 0.17)ml/s/1.73 sq.m Group C: 1.24 (+/- 0.21)ml/s/1.73 sq.m The mean values of GFR in different groups did not differ significantly. The mean values of FENa in different groups were as follows: Group A: 3.02 (+/- 1.59)% Group B: 2.05 (+/- 0.77)% Group C: 2.01 (+/- 1.17)% The mean value of FENa in group A was significantly higher than the mean value in group B (p < 0.01) and in group C (p < 0.01). The assembled findings support the idea that reduced tubular sodium reabsorption in the transplanted kidney (with a stabilized value of GFR) cannot be explained only as a manifestation of adaptation of tubular function as a result of the reduced number of functioning nephrons. The persisting osmotic sodium diuresis in the transplanted kidney must be viewed from the aspect of possibly impaired water preservation and the development of dehydration associated with a drop of GFR and must be differentiated from rejection.     

Improved survival of en bloc renal allografts from pediatric donors

PURPOSE: We developed a technical and immunological protocol to increase survival of renal transplants from pediatric donors. MATERIALS AND METHODS: En bloc kidneys (22) were procured from donors weighing 2 to 14 kg. (1 to 60 months old) and transplanted into adult recipients. In group 1 (12 patients) sequential therapy was used for kidneys with more than 35 hours of cold storage and immediate triple therapy (cyclosporine, azathioprine and prednisone) was used for those with less than 35 hours of cold storage. In group 2 (10 patients) OKT3 induction therapy was used. Mean followup was 4.7 years. RESULTS: Mean blood pressure at 1 and 4 years was not significantly different between the groups. Mean serum creatinine was not significantly different between the groups at 1 year but it was significantly less in group 2 at 4 years (1.9 +/- 1.0 versus 1.2 +/- 0.24 mg./dl., p <0.05). At 1 year of followup the complication rate was 75% in 9 of 12 patients in group 1, including 4 infections or leaks (2 lost), 6 rejections (3 lost) and 3 cases of thrombosis or hemorrhage, and 20% (p <0.01) in group 2 (1 patient had the hemolytic uremic syndrome leading to graft loss). Graft survival was significantly greater in group 2 at all 4 years of followup (p = 0.05). CONCLUSIONS: The success of pediatric en bloc renal transplantation can be enhanced by induction therapy in healthy recipients.     

The asystolic donor syndrome: transaminitis and thrombocytopenia after non-heartbeating renal transplantation

BACKGROUND: The use of kidneys from non-heartbeating donors (NHB) remains controversial. An increased incidence of delayed primary function and primary nonfunction is common. We report a characteristic syndrome of transaminitis and thrombocytopenia after NHB renal transplantation, which may be predictive of graft outcome. METHODS: Two case histories are presented, followed by a retrospective analysis of 38 NHB renal grafts performed at Guy's Hospital from 1988 to 1994. Changes in alanine aminotransferase (ALT) and platelet count were compared between recipients of kidneys from NHB and heartbeating donors (HB). To control for possible effects of antilymphocyte globulin (ALG), two matched control groups receiving HB kidneys with (n=32) and without (n=32) ALG were also compared. RESULTS: ALT was elevated in 32 of 38 (84%) of NHB recipients and 19 of 64 (30%) controls (P<0.001). Mean peak ALT was 172+/-20 U/L in NHB and 42+/-6 U/L in HB kidneys (P<0.001). Use of ALG did not influence mean peak ALT. Elevated ALT predicted impaired graft function (P<0.02) and was associated with an increased length of delayed primary function (P<0.001) and risk of transplant nephrectomy (P<0.05). Thrombocytopenia (<100 x 10(9) cells/L) occurred in 18 of 38 (47%) NHB recipients and in 20 of 64 (31%) controls (P<0.05). Mean nadir platelet count (x 10(9) cells/L) was 113+/-10 in NHB, 128+/-9 in HB with ALG, and 164+/-9 in HB without ALG (both P<0.05 vs. NHB). Patients who underwent graft nephrectomy (n=9) had a disproportionate fall in platelet count (mean nadir, 80+/-11 x 10(9) cells/L; P<0.05). CONCLUSIONS: Transaminitis and thrombocytopenia occur commonly after NHB kidney transplantation and are predictive of graft outcome. Recognition of these changes may assist the early management of NHB renal recipients, and also reduce investigation of "anomalous" results in this setting.     

Experimental transplantation of size-reduced, adult kidneys into pediatric recipients

BACKGROUND: Renal transplantation in infants is frequently complicated by graft thrombosis and accelerated rejection reactions. We herein tested the hypothesis that the amount of blood required to sustain normal perfusion of an adult renal allograft transplanted into a pediatric recipient would surpass the cardiac output and aortic blood flow of the recipient and that the ensuing low flow in full-size grafts (FSG) would induce a release of thrombogenic substances. METHODS: In a porcine renal transplant model, adult FSG were transplanted into pediatric recipients. Macro- and microhemodynamic as well as metabolic data were recorded. Surgically size-reduced grafts (RSG) served as controls. RESULTS: Donor weight was 55.1+/-4.8 kg and 9.6+/-0.9 kg for recipients. FSG weight was 122+/-16 g and 65+/-14 g for RSG. Blood flow in donor kidneys was 20% higher than the infrarenal aortic blood flow of recipients. After reperfusion, mean arterial pressure in recipients of FSG but not RSG dropped to 64 mmHg, despite an increase in cardiac output by 60%. FSG but not RSG were polyuric and proteinuric. The release of endothelin and thromboxane B2 into the circulation was higher from FSG when compared with RSG (P<0.05 for endothelin after 60 min; NS for thromboxane B2). CONCLUSIONS: After transplantation of FSG into pediatric recipients, the macrohemodynamic limitations of the recipient cause microcirculatory disturbances in the graft, which contribute to the release of vasoconstrictive and prothrombotic substances and an impaired early graft function. Some of those effects can be ameliorated by surgically size reducing the renal graft.     

Bone marrow transplantation for the treatment of alpha-mannosidosis

BACKGROUND: Traditionally, elderly donor kidneys have not been widely accepted for transplantation on the assumption of inferior performance. However, the United Network for Organ Sharing reports an increase in the number of elderly donors from less than 2% in 1982 to 24% in 1995. This trend is commensurate with the increase of older dialysis patients and an overall increase in the elderly population in the United States (1). Optimal utilization of these kidneys is essential to overcome the acute organ shortage. METHODS: In this study, we transplanted 25 kidneys from elderly donors (ages 56-72 years) into young adult recipients (ages 20-50 years) (group 1) over a 4-year period. We compared the results with matched recipients of young adult donor kidneys (group 2) with regard to long-term kidney function and graft survival. A pretransplant biopsy of elderly donor kidneys was carried out and a frozen section report was obtained. Only those kidneys showing glomerulosclerosis of less than 20% were accepted for transplantation. All cadaveric kidneys were preserved in University of Wisconsin solution. RESULTS: Pretransplant biopsies of elderly donor kidneys showed structural deficits, which included glomerulosclerosis in 85%, arteriolar and/or mesangial thickening in 75%, and interstitial lymphocyte infiltration in 30%. The mean serum creatinine was 2.4+/-0.74, 2.2+/-0.56, and 2.9+/-0.76 mg/100 ml in group 1 and 1.5+/-0.55, 2.3+/-2.24, and 1.7+/-0.62 in group 2 at 1, 3, and 5 years, respectively. The patient survival was 92%, 92%, and 88% in group 1, and 100%, 100%, and 100% in group 2 at 1, 3, and 5 years, respectively. The graft survival was 80%, 64%, and 56% in group 1 and 100%, 96%, and 88% in group 2 at similar time intervals. The differences in the serum creatinine and graft survival between the two groups were statistically significant (P < 0.05). CONCLUSIONS: Most of the elderly donor kidneys with structural deficits transplanted into young adults provided suboptimal function and inferior long-term graft survival. To maximize the utilization and optimize the survival of elderly donor kidneys, we propose transplantation of these kidneys into age-matched recipients with similar physiological requirements as those of donors, with regard to kidney function.     

Reduction of renal functional reserve in kidney transplant recipients: a possible role of arachidonic acid metabolism alterations

AIM: Renal functional reserve (RFR), resulting from an increase in glomerular filtration (GFR) after protein load, is a matter of debate. In kidney transplant recipients most studies have failed to show conclusive results, reporting either the absence, the reduction or the presence of renal reserve in normo-functioning kidneys. The aim of this study was to investigate RFR in kidney transplant patients as well as the possible hormonal vasoactive alterations underlying the reduction of renal reserve reported in some patients. PATIENTS AND METHODS: We studied 8 controls and 25 patients, the latter with no history of acute rejection for at least 12 months and GFR >50 ml/min. The 25 patients were divided into 2 groups based on the presence (10) or the absence (15) of RFR. RESULTS: Both the RFR group and the controls experienced a similar increase of GFR after oral protein load: 24.3 +/- 15.57% vs 24.4 +/- 10.8%. The group without RFR showed a paradoxical reduction of GFR after oral protein load: 13.3 +/- 13.2% (p <0.001). We analyzed the filtration fraction (FF) and observed that the group without RFR had higher values than the group with RFR and the controls: 0.35 +/- 0.11 vs 0.29 +/- 0.07 (p = 0.01) and vs 0.26 +/- 0.02 (p = 0.04). The hyperfiltration state observed in the group without RFR was sustained by a high level of thromboxane. The urine ratio TxB2/6ketoPgF1alpha was higher in the group without RFR than in the RFR group 0.78 +/- 0.2 vs 0.64 +/- 0.1 (p = 0.01). This ratio decreased only in the RFR group after a meat meal. In all the patients, changes of TxB2/6ketoPGF1alpha were inversely correlated to changes of GFR after a meat meal (r = -0.6, p = 0.01). CONCLUSIONS: In conclusion, these data demonstrate that kidney transplant recipients with good organ function can be grouped according to the presence of RFR. RFR appears to be inversely correlated with the TxB2/6ketoPGF1alpha ratio, and its decrease seems to be linked to the failure of thromboxane to decrease and prostacycline to increase after a meat meal.     

Double renal allografts successfully increase utilization of kidneys from older donors within a single organ procurement organization

BACKGROUND: In 1994, a policy of double renal allografting (DUAL) was used at two centers within our local organ procurement organization to increase utilization of kidneys from older donors that would otherwise be discarded. Both kidneys from an older donor (age > 60 years) were selectively transplanted into a single adult recipient. METHODS: The relative impact of a DUAL policy on the utilization of older donor kidneys is examined for the period of April 1994 to April 1996. Actual utilization is compared with the hypothetical case in which a DUAL policy is not present. RESULTS: In the actual setting, a total of 75 kidneys from older donors (> 60 years) were accepted for transplantation. Thirty-six kidneys were transplanted as singlets, and 16 additional kidneys were transplanted as DUAL renal allografts. Thus, a 44% increase in transplantable kidneys, and a 22% increase in patients transplanted with kidneys from older donors, was realized. In the actual setting, 23 older kidneys were discarded; without the DUAL policy, 39 kidneys would have been deemed untransplantable. When compared with the actual (n = 52) and hypothetical number of kidneys transplanted without a policy of DUAL transplantation (n = 36), the DUAL policy significantly increased the utilization of older donor kidneys (P = 0.01). The actuarial 1-year graft survival rate of the dual kidneys was 100%, with a mean follow-up of 11.1 +/- 2.9 months. Mean 6-month and 1-year serum creatinine level were 1.76 +/- 0.4 and 1.63 +/- 0.6 mg/dl, respectively. CONCLUSIONS: A DUAL policy significantly increased the number of older donor kidneys transplanted in a single organ procurement organization and reduced the rate of discard of older donor kidneys over a 2-year period. Long-term follow-up is necessary to substantiate satisfactory graft function in DUAL from older donors.     

Transplantation of pediatric en bloc cadaver kidneys into adult recipients

BACKGROUND: To maximize the renal donor pool, cadaveric pediatric en bloc kidneys have been transplanted as a dual unit by some transplant centers. We compared the short- and long-term outcomes of adult recipients of cadaveric pediatric en bloc renal transplants versus those of matched recipients of cadaveric adult kidneys. METHODS: Thirty-three adults who received pediatric en bloc kidney transplants between April 1990 and September 1997 were retrospectively identified and were compared with 33 matched adults who received adult cadaveric kidney transplants. The groups were identical for transplantation era, immunosuppression, recipient sex, race, cause of renal failure, mean weight, and follow-up duration (37.8 vs. 37.5 months). The mean recipient age study versus control was lower (36.3 vs. 48.9 years, P=0.0003). Results. There was no difference between the en bloc and adult donor groups in the 3-year patient survival rates (95% vs. 87%, P=0.16) or the 3-year graft survival rates (87.3% vs. 84.2%, P=0.35). Further, there was no difference in en bloc patient or en bloc graft survival time stratified by recipient age (14-44 vs. >45 years, P=0.11), en bloc donor age (<24 vs. >24 months, P=0.39), or recipient weight (<60, 61-75, >75 kg; P=0.60). Differences in serum creatinine (mg/dl) for the en bloc versus the control group at the time of discharge (3.0 vs. 7.8 mg/dl, P=0.06), at 1 year (1.4 vs. 2.0 mg/dl, P=0.06), and at 2 years (1.1 vs. 1.6 mg/dl, P=0.14) had dissipated by the time of the 5-year follow-up examination (1.1 vs. 1.6 mg/dl, P=0.14). Vascular complications were more prevalent in the en bloc group: renal vein thrombosis (one case), thrombosis of donor aorta (two cases), arterial thrombosis of one renal moiety (two cases), and renal artery stenosis (two cases). There were no differences between groups in delayed graft function, acute or chronic rejection, posttransplant hypertension, posttransplant protein-uria, or long-term graft function. CONCLUSIONS: Collectively, these data indicate that transplanting pediatric en bloc kidneys into adult recipients results in equivalent patient and graft survival compared with adult cadaveric kidneys. Further, the data also suggest that pediatric en bloc kidneys need not be strictly allocated based on recipient weight or age criteria.     

Improving results of pediatric renal transplantation

BACKGROUND: Outcome after renal transplantation in children has been variable. We undertook a retrospective study of our experience over the past five years. STUDY DESIGN: From January 1, 1988, to October 15, 1992, 60 renal transplantations were performed upon 59 children at the Children's Hospital of Pittsburgh. Twenty-eight (47 percent) of the kidneys were from cadaveric donors, and 32 (53 percent) were from living donors. The recipients ranged in age from 0.8 to 17.4 years, with a mean of 9.8 +/- 4.8 years. Forty-six (77 percent) recipients were undergoing a first transplant, while 14 (23 percent) received a second or third transplant. Eight (13 percent) of the patients were sensitized, with a panel reactive antibody of more than 40 percent. Eleven of the 14 patients undergoing retransplantation and seven of the eight patients who were sensitized received kidneys from cadaveric donors. Thirty-three (55 percent) patients received cyclosporine-based immunosuppression, and 27 (45 percent) received FK506 as the primary immunosuppressive agent. RESULTS: The median follow-up period was 36 months, with a range of six to 63 months. The one- and four-year actuarial patient survival rate was 100 and 98 percent. The one- and four-year actuarial graft survival rate was 98 and 83 percent. For living donor recipients, the one- and four-year actuarial patient survival rate was 100 and 100 percent; for cadaveric recipients, it was 100 and 96 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 95 percent for the living donor recipients and 96 and 69 percent for the cadaveric recipients. Patients on cyclosporine had a one- and four-year patient survival rate of 100 and 97 percent, and patients on FK506 had a one- and three-year patient survival rate of 100 and 100 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 85 percent in the cyclosporine group, while one- and three-year actuarial graft survival rates were 96 and 84 percent in the FK506 group. The mean serum creatinine level was 1.24 +/- 0.64 mg per dL; the blood urea nitrogen level was 26 +/- 13 mg per dL. The incidence of rejection was 47 percent; 75 percent of the rejections were steroid-responsive. The incidence of cytomegalovirus was 10 percent. The incidence of post-transplant lymphoproliferative disorder was 8 percent. None of the patients on cyclosporine were able to be taken off prednisone; 56 percent of the patients receiving FK506 were taken off prednisone successfully. Early growth and development data suggest that the patients receiving FK506 off prednisone had significant gains in growth. CONCLUSIONS: These results support the idea that renal transplantation is a successful therapy for end-stage renal disease in children. They also illustrate the potential benefits of a new immunosuppressive agent, FK506.     

The central visual field in homonymous hemianopia. Evidence for unilateral foveal representation

Renal functional reserve (RFR) after an oral protein load was evaluated in 36 cyclosporine-treated children following kidney transplantation (Tx), in 15 kidney donors (Don), and in 15 children with single kidneys (Nx/Ag). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by clearances of inulin (and creatinine) and para-aminohippurate during water diuresis. Baseline and stimulated GFR and ERPF were determined and RFR was calculated as the difference between stimulated and baseline values. Baseline GFR and ERPF in Tx were lower than in Don and Nx/Ag. Both GFR and ERPF increased significantly in all groups from baseline to stimulated values. RFR GFR was 23% +/- 3%, 20% +/- 3% and 15% +/- 3% in Tx, Don, and Nx/Ag and RFR ERPF 35% +/- 4% in Tx, which was significantly higher than 20% +/- 4% and 15% +/- 3% in the two other groups respectively. Stimulated GFR and ERPF in Tx correlated with kidney length. No differences were seen in recipient-donor pairs, except for higher fractional increases of ERPF in recipients. There was no correlation between RFR measured by clearance of creatinine and clearance of inulin. In conclusion, cyclosporine-treated children following renal Tx were found to have a renal reserve capacity.     

Long-term improvement in renal function after cyclosporine reduction in renal transplant recipients with histologically proven chronic cyclosporine nephropathy

BACKGROUND: Chronic cyclosporine (CsA) nephropathy, which has been unequivocally documented in recipients of heart, heart-lung, liver, or bone marrow transplants, as well as in nontransplant situations, usually results in a progressive deterioration of renal function. In this study, we assessed the potential reversibility of chronic CsA nephropathy in renal transplant recipients. PATIENTS AND METHODS: Twenty-three renal transplant patients with biopsy-proven CsA nephropathy associated with long-term CsA administration (27+/-4 months) were followed up for more than 2 years after CsA reduction (18/23 patients) or withdrawal (5/23 patients) and addition of azathioprine. Changes in effective renal plasma flow and glomerular filtration rate were assessed before and 2 years after CsA reduction, whereas serum creatinine, proteinuria, blood pressure, and CsA concentrations were monitored up to 5 years. RESULTS: At 2-year follow-up, glomerular filtration rate increased from 40+/-3 to 47+/-4 (P<0.05) and effective renal plasma flow from 217+/-23 to 244+/-24 ml/min/1.73 m2 (NS). Mean arterial pressure significantly decreased from 98.7+/-2.9 to 93.1+/-2.7 mmHg (P<0.05). There was no significant change in renal vascular resistance, filtration fraction, or albumin excretion. A significant decrease in serum creatinine was also observed during the whole follow-up (73+/-6.5 months). CsA reduction was followed by only one episode of acute reversible rejection; chronic rejection developed in three patients 2 years or later after CsA reduction. CONCLUSIONS: These data suggest that CsA nephropathy participates in graft dysfunction in a small group of renal transplant recipients. In addition, graft dysfunction may be reversible when CsA dosage is reduced early after diagnosis of chronic CsA nephropathy.     

The use of bilateral adult renal allografts - a method to optimize function from donor kidneys with suboptimal nephron mass

Alternatives to traditional organ donor usage has allowed expansion of the organ donor pool to help compensate for the increasing disparity between recipients and donors. The use of bilateral adult renal transplants is a novel idea to salvage older donor kidneys with suboptimal nephron mass that would otherwise be destined for discard. Ten renal transplants were performed utilizing both kidneys from adult cadaver donors with diminished nephron mass determined by calculated glomerular filtration rate or biopsy evidence of significant glomerulosclerosis (>10%). Nine of ten (90%) recipients have satisfactory renal function at a mean follow-up of 7 months. The single case of graft failure was due to documented medical non-compliance. Mean serum creatinine at 6 months was 1.5 mg/dl. Mean measured creatinine clearance was 43.2+/-3.4. These preliminary findings suggest that the use of bilateral renal transplants provide satisfactory early function and allows salvage of older donor kidneys with suboptimal nephron mass.     

When should expanded criteria donor kidneys be used for single versus dual kidney transplants?

BACKGROUND: To increase the utilization of cadaveric donor kidneys, we have recently expanded our acceptable criteria to include aged donors (frequently with a history of hypertension), by selectively using both donor kidneys (dual transplant) into a single recipient. METHODS: To define when these expanded criteria donor (ECD) kidneys should be used as a single versus a dual kidney transplant, we retrospectively reviewed 52 recipients of ECD kidneys that had been turned down by all other local centers between 1/1/95 and 11/15/96. Fifteen patients received dual transplants, whereas the remaining 37 received single kidneys. Of the dual kidney recipients, 14 of 15 ECD were > or = 59 years of age, 10 of 15 were hypertensive, and 9 of 15 were both. Of the single recipients, 11 of 37 ECD were > or = 59 years of age, 11 of 37 were hypertensive, and 7 of 37 were both. All patients received cyclosporine-based triple-drug therapy. We compared seven donor (D) and sixteen recipient outcome variables in single versus dual kidney transplants as subgrouped by: (1) donor admission creatinine clearance (D-AdC(Cr)) < 90 ml/min; (2) D-age > or = 59 years; and (3) cold storage (Cld Stg) < or > 24 hr. RESULTS: In the group with D-AdC(Cr) < 90, there was a significantly higher incidence of delayed graft function (DGF) in single versus dual recipients (9 of 20 [45%] vs. 1 of 11 [9%]; P=0.04) and worse early graft function based upon mean serum creatinine at 1 and 4 weeks (5.3+/-3.3 and 2.8+/-2.0 vs. 1.7+/-0.6 and 1.4+/-0.5 mg] dl; P<0.05). In the group with D-age > or = 59, recipients of single kidneys had significantly higher mean serum creatinine at 1, 4, and 12 weeks versus recipients of dual kidneys (5.1+/-3.3, 3.4+/-2.1, 2.8+/-1.5 versus 2.8+/-2.5, 1.5+/-0.6, 1.6+/-0.5 mg/dl; P<0.05). Cld Stg time also had an impact on DGF and early outcome. Recipients of dual kidneys stored less than 24 hr had a significantly lower incidence of DGF versus single kidneys stored more than 24 hr (10% vs. 46%; P<0.05) and better early graft function based on mean serum creatinine at 1, 4, and 12 weeks (1.9+/-0.8, 1.3+/-0.4, 1.5+/-0.2 vs. 6.6+/-3.4, 3.0+/-1.6, 2.9+/-1.9 mg/dl; P<0.05). The overall 1-year patient and graft survivals were 96% and 81% vs. 93% and 87% (P=NS) in recipients of single ECD versus dual ECD kidneys. CONCLUSIONS: In conclusion, we believe that kidneys from ECD with D-AdC(Cr) < 90 ml/min and D-age > or = 59 should be used as dual kidney transplants, keeping the Cld Stg time at < 24 hr to minimize the effect of Cld Stg on early graft function.     

Outcome of en bloc and single kidney transplantation from very young cadaveric donors

BACKGROUND: The optimal use of very young cadaveric kidneys (from donors less than 4 years old) remains controversial. High rates of technical complications and poor functional results compared with adult donor kidneys have been reported. The use of en bloc transplantation to overcome these problems has been advocated, although en bloc transplantation halves the number of potential transplants from very young donors. METHODS: We studied the technical and functional results of 91 transplants from very young donors performed at our institution between 1984 and 1995. This included 59 single and 22 en bloc procedures involving first transplants and 7 single and 3 en bloc procedures involving retransplantation. Individual surgeon preference dictated the use of either the single or en bloc technique. Kidneys smaller than 6 cm tended to be transplanted en bloc, and lighter patients were generally given preference for receiving pediatric kidneys. Patients received sequential cyclosporine-based quadruple immunosuppression. RESULTS: En bloc kidneys had a 1-year and 5-year graft survival of 82% and 70%, respectively. Single kidneys had a 1-year and 5-year graft survival of 64% and 40%. Kidneys that avoided acute rejection episodes and that were transplanted into heavier or male recipients had better long-term survival. Kidneys from donors less than 2 years old did poorly whether transplanted en bloc or singly. Better HLA matching improved short-term, but not long-term, graft survival, whereas cold ischemic time did not have statistically significant association with differences in graft survival. Eleven percent of the transplants had ureteral leaks, but only one kidney was lost. Ten transplants had vascular complications leading to graft loss, whereas two episodes of arterial stenosis were successfully treated with percutaneous angioplasty. CONCLUSIONS: En bloc transplantation optimizes the outcome of transplantation with very young kidneys. We recommend induction therapy and cyclosporine immunosuppression with cyclosporine levels similar to adult target levels to minimize rejection episodes and, thus, improve outcome. These kidneys should be distributed nationally, because better HLA matching is associated with improved short-term graft survival. Our high ureteral leak rate indicates that alternatives to unstented ureteroneocystostomy should be considered.     

En bloc renal transplant from infant donors to adults

OBJECTIVE: To analyze the medium-term outcome of en bloc transplantation of pediatric kidneys into adult patients, including the incidence and type of surgical complications. METHODS: From November 1991 to December 1997, we performed 37 en bloc transplantation of pediatric kidneys into adult patients. The kidneys were harvested from donors less that 3 years old and/or weighing 15 kg. The mean follow-up was 24 months. Grafting was achieved by end-to-side anastomosis of the donor cava to the receptor external iliac and the aortic patch to the external iliac artery. RESULTS: Three grafts failed, probably due to hilar torsion; the remaining were initially functioning well. Seven transplant removal were performed; 6 were due to thrombosis. The actuarial graft survival was 89.1% at one month, 80.83% at 12 months and 80.83% at 24 months. CONCLUSIONS: The medium-term results of en bloc transplantation of pediatric kidneys into adult patients were excellent and demonstrate the efficacy of this type of grafts. Arterial and venous thrombosis were the most important complications, quantitatively and qualitatively.     

High-dose rate iridium192 afterloading therapy in combination with external beam irradiation for localized prostate cancer

The number of donors aged 60 years and over has increased. This study examined discard rates and transplant outcomes in organs recovered from older donors. Data were obtained using a standard tool for donors aged 60 years and older during 1993 and 1994 and included demographics, medical history, use of vasopressors, renal/liver function studies, organ disposition, biopsy findings, and recipient organ function. Of 58 kidneys recovered, 24 were transplanted, 26 were used for research, and 8 were discarded. Of 14 livers recovered, 11 were transplanted, 1 was used for research, and 2 were discarded. Sixty-three percent of kidney recipients had immediate function; 79% at 30 days. Nine liver recipients had immediate function; 6 at 30 days, with 1 graft lost. Results show that kidneys and livers can be transplanted from older donors with positive outcomes. Factors such as medical history, use of vasopressors, and organ function studies may help predict organ disposition and function.     

Ablation of irreversibly rejected renal allograft by embolization with absolute ethanol: a new clinical application

Surgical allograft nephrectomy has been the conventional therapy for removing failed kidney allografts when clinical manifestations of graft intolerance appear. However, removal of a transplanted kidney is an extensive surgical procedure. On the other hand, transcatheter vascular embolization (TVE) has proven useful in ablating organs and could be applied to renal transplant ablation. The aim of this study was to present the results of TVE for the treatment of graft intolerance syndrome (GIS) in failed allograft kidneys. Transcatheter vascular embolization was performed in 14 allograft recipients (33 +/- 13 years of age; 10 men and four women) affected by GIS after irreversible kidney allograft failure. Graft intolerance syndrome was diagnosed by fever (93%), hematuria (50%), graft pain (36%), flu-like symptoms (29%), and increased graft size (29%). Absolute ethanol (0.1 mL/kg body weight) was injected in the allograft artery, and in seven patients a stainless steel coil was left in the renal artery following ethanol injection. All patients showed clinical disappearance of the GIS. No major complication occurred, although a postembolization syndrome of pain, fever, hematuria, numbness, and paresthesia of the affected area appeared in 11 of the 14 patients. After 2 to 56 months of follow-up no late complications occurred, with the exception of a graft abscess formation in one patient after 6 months of embolization. Subsequent transplantectomy was uneventful. In conclusion, TVE is a safe and effective method for kidney graft ablation, and it may become an alternative treatment for GIS following irreversible rejection.