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Background: There is uncertainty about the long-term risks of living kidney donation. Well-designed studies with controls well-matched on risk factors for kidney disease are needed to understand the attributable risks of kidney donation., Methods: The goal of the Minnesota Attributable Risk of Kidney Donation (MARKD) study is to compare the long-term (> 50 years) outcomes of living donors (LDs) to contemporary and geographically similar controls that are well-matched on health status. University of Minnesota (n = 4022; 1st transplant: 1963) and Mayo Clinic LDs (n = 3035; 1st transplant: 1963) will be matched to Rochester Epidemiology Project (REP) controls (approximately 4 controls to 1 donor) on the basis of age, sex, and race/ethnicity. The REP controls are a well-defined population, with detailed medical record data linked between all providers in Olmsted and surrounding counties, that come from the same geographic region and era (early 1960s to present) as the donors. Controls will be carefully selected to have health status acceptable for donation on the index date (date their matched donor donated). Further refinement of the control group will include confirmed kidney health (e.g., normal serum creatinine and/or no proteinuria) and matching (on index date) of body mass index, smoking history, family history of chronic kidney disease, and blood pressure. Outcomes will be ascertained from national registries (National Death Index and United States Renal Data System) and a new survey administered to both donors and controls; the data will be supplemented by prior surveys and medical record review of donors and REP controls. The outcomes to be compared are all-cause mortality, end-stage kidney disease, cardiovascular disease and mortality, estimated glomerular filtration rate (eGFR) trajectory and chronic kidney disease, pregnancy risks, and development of diseases that frequently lead to chronic kidney disease (e.g. hypertension, diabetes, and obesity). We will additionally evaluate whether the risk of donation differs based on baseline characteristics., Discussion: Our study will provide a comprehensive assessment of long-term living donor risk to inform candidate living donors, and to inform the follow-up and care of current living donors., (© 2023. The Author(s).)

Kidney transplantation entails well-coordinated complex care delivery. Patient-provider cultural and linguistic discordance can lead to healthcare disparities. We analyzed kidney transplantation outcomes among our institution's Hmong recipients using a retrospective cohort study. From 1995 to 2015, 2164 adult (age ≥18) recipients underwent kidney transplantation at our institution; 78 self-identified as Hmong. Survival rates were analyzed and compared to Caucasian recipients (n = 2086). Fifty (64.1%) Hmong recipients consistently requested interpreters. Mean follow-up was 9.8 years for both groups. Hmong recipients (N = 78) were on average younger at transplant (45.7 vs 49.7 years; P = 0.02), more likely to be female (56% vs 38%; P = 0.001), and had higher gravidity (5.0 vs 1.9 births; P < 0.001). There were 13 (16.7%) Hmong living donor recipients, who were younger (32.8 vs 42.9 years; P = 0.006) at transplant compared to Caucasians (1429, 68.5%). Hmong 1- and 5-year patient survival was 100%; Caucasians, 97.1% and 88% (P < 0.001). Hmong 1- and 5-year graft survival was 98.7% and 84.9%; Caucasians 94.8% and 80.9% (P = 0.013). One- and 5-year rejection-free survival showed no difference (88.9% vs 82.4%; 86.7% vs 83.4%, P = 0.996). Despite cultural and linguistic differences between Hmong recipients and providers, we found no evidence of inferiority in KT outcomes in the Hmong population., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Suboptimal immunosuppression after kidney transplantation contributes to toxicity and loss of efficacy. Little is known regarding the impact of intra-patient variability of tacrolimus (TAC) doses and troughs in the early post-transplant period or the influence of genetic variants on variability., Methods: Coefficients of variation (CV) of TAC troughs and doses of 1226 European American (EA) and 246 African American (AA) adult recipients enrolled in DeKAF Genomics were compared for association with acute rejection and graft failure. Additionally, the influence of recipients' number of CYP3A5 loss-of-function alleles was assessed., Results: Acute rejection was associated with greater CV of dose in AA (P < 0.001) and EA recipients (P = 0.012). Graft failure was associated with a greater CV of dose (P = 0.022) and trough (P < 0.001) in AA, and higher CV of trough (P = 0.024) in EA recipients. In EA, CYP3A5 loss-of-function alleles were associated with decreased CV of trough (P = 0.0042) and increased CV of dose (P < 0.0001)., Conclusion: CYP3A5 loss-of-function alleles influence intra-patient TAC trough and dose variability. High variability of TAC dose increases risk of acute rejection. High variability of TAC trough increases risk of graft failure. Early clinical recognition of TAC dose and trough variability may improve patient management and outcomes., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: KT recipients have increased the risk of CVD. The incidence of post-transplant CVEs among pediatric recipients has not been well-characterized., Patients and Methods: Between 1963 and 2015, 884 pediatric (age: 0-17 years old) recipients received 1058 KTs at our institution. The cumulative incidence of CVEs was analyzed. Statistical models were used to estimate risk factors for developing post-transplant CVEs., Results: Overall median patient survival was 33 years (IQR: 18.7-47). A total of 362 CVEs occurred in 161 (18.3%) patients at a median age of 20.5 years. Arrhythmias (18%) were most common. Cumulative risk of post-transplant CVEs was 9% at 10 years, 17% at 20 years, 25% at 30 years, and 36% at 40 years. Development of post-transplant CVEs was associated with increased mortality (HR 2.25 [95% CI 1.61-3.14]); of those who developed a CVE and died, 22/51 (43.1%) died of CVD. Multivariable risk factors for post-transplant CVEs included a history of pretransplant CVD (aHR 1.92 [1.18-3.13] and graft failure (4.57 [3.13-6.67])., Discussion: A pretransplant history of CVD and a failed graft are significant risk factors for the development of post-transplant CVE. CVD increases the risk of post-transplant death or graft loss., (© 2018 Wiley Periodicals, Inc.)

Background: Living donor segmental pancreas transplants (LDSPTx) have been performed selectively to offer a preemptive transplant option for simultaneous pancreas-kidney recipients and to perform a single operation decreasing the cost of pancreas after kidney transplant. For solitary pancreas transplants, this option historically provided a better immunologic match. Although short-term donor outcomes have been documented, there are no long-term studies., Methods: We studied postdonation outcomes in 46 segmental pancreas living donors. Surgical complications, risk factors (RF) for development of diabetes mellitus (DM) and quality of life were studied. A risk stratification model (RSM) for DM was created using predonation and postdonation RFs. Recipient outcomes were analyzed., Results: Between January 1, 1994 and May 1, 2013, 46 LDSPTx were performed. Intraoperatively, 5 (11%) donors received transfusion. Overall, 9 (20%) donors underwent splenectomy. Postoperative complications included: 6 (13%) peripancreatic fluid collections and 2 (4%) pancreatitis episodes. Postdonation, DM requiring oral hypoglycemics was diagnosed in 7 (15%) donors and insulin-dependent DM in 5 (11%) donors. RSM with three predonation RFs (oral glucose tolerance test, basal insulin, fasting plasma glucose) and 1 postdonation RF, greater than 15% increase in body mass index from preoperative (Δ body mass index >15), predicted 12 (100%) donors that developed postdonation DM. Quality of life was not significantly affected by donation. Mean graft survival was 9.5 (±4.4) years from donors without and 9.6 (±5.4) years from donors with postdonation DM., Conclusions: LDSPTx can be performed with good recipient outcomes. The donation is associated with donor morbidity including impaired glucose control. Donor morbidity can be minimized by using RSM and predonation counseling on life style modifications postdonation.

Objectives: To evaluate quality of life (QOL) in kidney transplant recipients aged 65 and older, identify predictors of impaired physical and mental QOL cross-sectionally and compare QOL over time with that of younger transplant recipients and general population controls., Design: Comparison of serial Medical Outcomes Study 36-item Short-Form Survey (SF-36) QOL scores in transplant recipients aged 65 and older with those of transplant recipients younger than 65 and with those of general population controls from the National Health Measurement Study (NHMS)., Setting: University of Minnesota., Participants: Individuals aged 65 and older (n = 150) and younger than 65 (n = 1,544) who received a primary kidney transplant between 1963 and 2009., Measurements: Two-sample t-tests and logistic regression were used to assess the risk of significant impairment in physical and mental QOL, defined as 1 standard deviation below the general population norms (<40 points) for the SF-36 Physical (PCS) and Mental Component Subscale (MCS) scores., Results: PCS scores were 39.3 for transplant recipients aged 65 and older, 43.5 for recipients younger than 65, and 49.2 for NHMS controls (P < .005 for each pairwise comparison). MCS scores were 54.6 for transplant recipients aged 65 and older, 51.0 for recipients younger than 65, and 53.8 for NHMS controls (P < .005 for ≥ 65 vs <65 and NHMS vs <65). These scores did not change significantly from the first (3.6 years after transplant) to the last (6.2 years after transplant) survey. Longer time since transplantation in elderly participants was associated with having significantly impaired physical QOL, but no predictors were associated with significantly impaired mental QOL. In younger recipients, rejection, diabetes mellitus, delayed graft function, coronary artery disease, and longer time on dialysis were associated with impaired physical QOL. Rejection, smoking, diabetes mellitus, and longer time on dialysis were predictors of impaired mental QOL., Conclusion: Physical QOL is lower in elderly recipients but mental QOL is maintained and is higher than in younger recipients., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Background and Objectives: Rapid discontinuation of prednisone after kidney transplantation potentially allows for minimization of steroid-related side effects. Although intermediate-term data with rapid discontinuation of prednisone have been promising, concern still exists regarding long-term outcomes. The 10-year experience is reported herein., Design, Setting, Participants, & Measurements: Between October 1, 1999 and December 31, 2010, 1241 adult primary kidney transplants (791 living donor and 450 deceased donor) were performed using a protocol in which prednisone is discontinued after postoperative day 5. The 10-year actuarial recipient and graft survival rates and prednisone-related side effects were studied., Results: Ten-year actuarial patient survival was 71% for living donor transplants and 62% for deceased donor transplants; 10-year graft survival was 61% for living donor transplants and 51% for deceased donor transplants, and was comparable to 10-year Scientific Registry of Transplant Recipients national data. Ten-year death-censored graft survival was 79% for living donor transplants and 80% for deceased donor transplants. Ten-year acute rejection rates were 25% for deceased donor transplants and 31% for living donor transplants; 10-year chronic rejection (interstitial fibrosis/tubular atrophy) rates were 39% for deceased donor transplants and 47% for living donor transplants. For nondiabetic recipients of living donor or deceased donor allografts, the incidence of new-onset diabetes was significantly lower than in historical controls on prednisone (P<0.001). We also found significantly reduced rates of cataracts, avascular necrosis, and cytomegalovirus infection in some subgroups., Conclusions: Prednisone-related side effects can be minimized in a protocol incorporating rapid discontinuation of prednisone for maintenance immunosuppression. Ten-year patient and graft outcomes remain acceptable.

To better understand the implications for considering delayed graft function (DGF) as a performance measure, we compared outcomes associated with a 2- to 3-fold difference in the incidence of DGF at two transplant centers. We analyzed 5072 kidney transplantations between 1984 and 2006 at the University of Minnesota Medical Center (UMMC) and Hennepin County Medical Center (HCMC). In logistic regression the adjusted odds ratio for DGF at HCMC versus UMMC was 3.11 (95% Confidence Interval [CI]= 2.49-3.89) for deceased donors and 2.24 (CI = 1.45-3.47) for living donors. In Cox analysis of 4957 transplantations, slow graft function (SGF; creatinine >or=3.0 mg/dL [230 micromol/L] on day 5 without dialysis) was associated with graft failure at UMMC (Relative Risk [RR]= 1.43, CI = 1.25-1.64), but not HCMC (RR = 0.99, CI = 0.77-1.28). RR's of DGF were similar at both centers. Thus, the lower incidence of DGF at UMMC likely resulted in a higher incidence and higher risk of SGF compared to HCMC. Indeed, graft survival for recipients with DGF at HCMC was similar (p = 0.3741) to that of recipients with SGF at UMMC. We conclude that dialysis per se is likely not a cause of worse graft outcomes. A better definition is needed to measure early graft dysfunction and its effects across transplant programs.

The outcome of pregnancy in kidney donors has generally been viewed to be favorable. We determined fetal and maternal outcomes in a large cohort of kidney donors. A total of 2102 women have donated a kidney at our institution; 1589 donors responded to our pregnancy surveys; 1085 reported 3213 pregnancies and 504 reported none. Fetal and maternal outcomes in postdonation pregnancies were comparable to published rates in the general population. Postdonation (vs. predonation) pregnancies were associated with a lower likelihood of full-term deliveries (73.7% vs. 84.6%, p = 0.0004) and a higher likelihood of fetal loss (19.2% vs. 11.3%, p < 0.0001). Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p < 0.0001), proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia (5.5% vs. 0.8%, p < 0.0001). Women who had both pre- and post-donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies. In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.

As results after transplants continue to improve, the burden associated with long-term immunosuppression and the complications associated with these agents become more significant. Recent trends in immunosuppression minimization strategies show that prednisone minimization protocols are not associated with significantly increased acute rejection or chronic graft dysfunction. With long-term data now available, we can see that the majority of such recipients (>80%) can remain prednisone free. There seems to be no compromise in terms of long-term results, and a definite improvement with regard to steroid-related and viral complications. These protocols can be used in minorities, children, and higher immunologic risk kidney transplant recipients, and in liver and pancreas recipients. The question of what is the ideal maintenance agent to couple with prednisone-free regimes remains unclear, and it may be that different agents may be better suited for different groups of recipients. Why is prednisone minimization now possible, when previous attempts were unsuccessful? Several explanations are possible. Early attempts concentrated on steroid withdrawal - removing prednisone once the patient had been on therapy for at least 3 months (18-20). Outcomes differ between studies reporting rapid prednisone withdrawal and those reporting prednisone withdrawal at a later time, but it is not clear why rapid prednisone withdrawal has succeeded and late prednisone withdrawal has failed. Other factors may include the routine use of polyclonal antibody for induction therapy and the use of newer immunosuppression agents such as MMF, TAC, and SRL. Finally, the newer trials of prednisone minimization have been performed in a different era, a time when results have improved as has our understanding of the risk factors associated with long-term graft survival. While ongoing follow-up of this group of patients will continue to be important, our experience suggests that maintenance prednisone is likely not required for the majority of kidney transplant recipients today.

At the University of Minnesota, we have defined 'nondirected donation' as organ donation by a volunteer who offered to donate an organ to anyone on the cadaver waiting list. From October 1, 1997, through October 31, 2003, we have had 360 inquiries about nondirected donation, have completed 42 detailed nondirected donor (NDD) evaluations for kidney donation, and have performed 22 NDD transplants. We herein review our program policies and how they have evolved, describe our evaluation and the motivation of our potential donors, summarize the outcome of NDD transplants, and raise issues requiring further attention and study. Our experience continues to support nondirected donation for kidney transplants.

Immunosuppressive protocols at the University of Minnesota have evolved from identical immunosuppression for all recipients (prednisone, azathioprine, and antilymphocyte globulin) to differing protocols for living (triple therapy) and cadaver (sequential therapy) donor recipients, and then to our current protocol in which all recipients receive induction therapy with rapid discontinuation of prednisone. At the same time, progress has been made in the prevention and treatment of cytomegalovirus infection along with numerous parallel improvements in patient care, including in anesthesia, dialysis, and intensive care unit care. The net result has been an incremental improvement in recipient and graft survival.

From October 1, 1997 through November 30, 2003, the University of Minnesota received 362 inquiries from potential NDDs. Of these, 53 (15%) then underwent partial or full donor evaluation at our transplant center. Of these 53 potential NDDs, 24 have been accepted (23 donated, and one donation is pending), 23 were denied (15 for medical reasons, 8 for psychosocial reasons), and 6 chose not to pursue donation. Most of our potential NDDs were motivated by altruistic reasons. Their decision-making process was not impulsive or instantaneous, but rather rational and deliberate. They were self-educated about donation before contacting our transplant center. After donation, all 23 of our NDDs said they were glad they donated and were grateful for the opportunity to help another. Many desired to become involved in the transplant community by promoting donation. All NDDs who heard from their recipient appreciated the contact and the chance to learn how the recipient was doing posttransplant. An NDD program clearly mandates a dedicated donor team and additional time and resources, given the high number of inherent practical, logistical, and ethical issues. Our protocol has been a work in progress and continues to evolve with our ever-growing experience. Transplant centers interested in using NDDs must develop NDD protocols to address specific issues and must examine their available staffing and resources.

Between 6/1963 and 12/1998, 5,069 kidney transplants were done at the University of Minnesota. Of these, about half have been living donor, half cadaver. The majority (83%) have been primary transplants. Recipients were grouped in 6 eras based on changes in our immunosuppressive protocols--6/63-12/67 (n = 98); 1/68-7/79 (n = 1,188); 8/79-6/84 (n = 789); 7/84-9/90 (n = 1,006); 10/90-12/95 (n = 1,050; 1/96-12/98 (n = 718)--and their outcomes were compared. Recent eras contained a higher proportion of recipients aged > 50. Since the inception of the program, there has been a steady improvement in actuarial patient survival, graft survival, and death-censored graft survival. Short-term outcome for primary and retransplant recipients has been similar; however, long-term outcome seems worse for retransplant recipients. Importantly, acute rejection and infectious death have become rare causes of graft loss. Chronic rejection and death with function (most often due to a cardiovascular event) have become the predominant causes of graft loss. Recent changes in immunosuppressive protocols (Era VI) have included more aggressive attempts to maintain CsA levels > 150 ng/ml (by HPLC) in the first 3 months and the substitution of mycophenolate mofetil for azathioprine. As a result, the incidence of acute and chronic rejection has decreased and graft survival has improved.

Clinical renal transplantation is limited by the number of cadaver and living related donors. The use of kidneys from older donors and non-first-degree relatives, including grandparents, has increased the supply of organs for transplantation. The purpose of this study was to assess donor and recipient outcomes after living related renal transplants between grandparent donors and grandchild recipients. Fifteen living related renal transplants using grandparent donors were performed at the University of Minnesota from 1971 to 1995. All medical records from donors and recipients were retrospectively reviewed. In addition, all grandparents or, in one case, a surviving family member were contacted to obtain current information on medical health and feedback about the donation process. A current serum creatinine (Cr) level was obtained from 14 donors and 15 recipients. Statistical calculations were performed using the SAS system. Eleven grandmothers and four grandfathers, 34-70 yr old (mean, 55 yr) at the time of transplantation, donated a kidney to 15 grandchildren with end-stage renal disease. There were no major surgical complications in either group. One donor died from unrelated causes; the other 14 donors are alive with stable renal function (1.3 +/- 0.3 mg/dL). Of 15 transplanted kidneys, 10 remain functional (Cr 1.3 +/- 0.7 mg/dL) with 2- and 5-yr graft survival rates of 76% and 63%, respectively. Our results indicate that healthy grandparents provide an excellent population for living related kidney donation.

This review describes the immediate and long-term risks to kidney donors. We reviewed their perioperative morbidity and mortality as well as their quality of life after donation. The overall mortality in our series was zero. Nationally, donor mortality has been estimated to be 0.03% (5). Our overall complication rate was 8.2% with only 2 (0.2%) complications considered to be major (16). Complications were associated with male sex, body weight > or = 100 kg, and inadvertent entry into the pleura during the donor operation. Most of our donors were discharged from the hospital in < 5 days. Risk factors for a longer hospital stay were age 50 or older and an operative time of 4 hours or more. The average donor quality of life after donation, as measured by the SF-36, was better than that of the general US population. This finding persisted for years after donation. The vast majority of our donors found the experience to be very rewarding and would readily donate again if it were possible. However, 4% were dissatisfied and regretted their decision to donate a kidney; these were most likely to be donors other than a first-degree relative and donors whose recipient died within the first posttransplant year. Living donation of kidneys appears to be relatively safe, with very few physical and psychologic complications. It may even improve the donor's quality of life. Living donors are an underutilized source of kidneys. We continue to advocate and encourage living kidney donation.

Unlabelled: We analyzed 420 kidney retransplants at the University of Minnesota, 87 of which did and 333 which did not share HLA mismatches with the previous transplant. There was no difference in outcome. We conclude that exceptions to routine HLA matching policies do not have to be made for kidney retransplants., Objective: To determine if the kidney graft functional survival rate for retransplants is influenced by presence of HLA mismatches in common with the previous (failed) transplant., Summary Background Data: Kidney retransplants have a lower function rate than primary grafts. An anamnestic response to HLA antigens shared with the previous donor could be one factor responsible, but reports in the literature are conflicting., Methods: Of 420 kidney retransplants with HLA information done at the University of Minnesota, 87 shared > or = 1 HLA antigens specifically mismatched with the previous donor (63 cadaver and 24 living donor retransplants), while 333 did not (247 cadaver, 86 living donor). Patient and graft survival rates were calculated by life-table analysis for recipients with vs. without repeat mismatches, with the significance of differences determined by the Lee-Desu statistic., Results: Patient and kidney graft retransplant survival rate curves were not significantly different (p > or = 0.41) for those exposed or not exposed to the same HLA mismatches as before. At 2 years, 70% vs. 61%, respectively, of cadaver grafts and 71% vs. 78%, respectively, of living donor grafts were functioning., Conclusions: The probability of a successful outcome with a kidney retransplant is no different for patients who do than for those who do not receive an organ sharing HLA mismatches with the previous donor. Exceptions to routine HLA matching policies do not need to be made for kidney retransplants.

We reviewed urologic complications of 1183 consecutive primary or secondary renal transplants performed with bladder anastomoses at the University of Minnesota Hospital between 1985 and 1993. The Politano-Leadbetter (PL) technique of ureteroneocystostomy was used in 410 patients; the multistich (MS) extravesical technique modified from the methods of Witzel, Sampson, and Lich in 295; and the extravesical single-stitch (SS) technique in 478. Urologic complications occurred in 81 patients (6.8%). Of these complications, 68 (5.7%) were early (< 4 months) and 13 (1.1%) late; 32 (7.8%) were after PL, 17 (5.8%) after MS, and 32 (6.7%) after SS. A total of 13 patients had an anastomotic leak, 7 (1.7%) after PL, 4 (1.4%) after MS, and 2 (0.0004%) after SS; 49 patients had a ureterovesical obstruction, 16 (4.0%) after PL, 12 (4.0%) after MS, and 21 (4.2%) after SS; 5 patients had a ureteropelvic obstruction, 2 (0.5%) after PL, 2 (0.7%) after MS, and 1 (0.2%) after SS; and 14 patients had hematuria, 7 (1.7%) after PL, 1 (0.34%) after MS, and 6 (1.3%) after SS. Of the 81 patients with urologic complications, one (1%) resolved spontaneously; 30 (37%) were treated with temporary percutaneous nephrostomy, 17 (21%) with dilatation and stent; the 14 (17.3%) with hematuria were treated via cystoscopy; 19 (23%) required reoperation. Only 2 (2.5%) patients lost their graft. For both cadaver and living donor recipients, there was no difference between techniques for early and late complications of leakage, stricture, and hematuria. Each technique has certain advantages and each should be in every surgeon's repertoire.

The prevalence of hyperlipidemia in adolescents and young adults who are long-term survivors of pediatric renal transplantation with stable graft function has not previously been examined. We studied 33 renal transplant recipients aged 5 to 23 years, who were an average of 7.4 years (range 3 to 11 years) post-transplant. We found hypercholesterolemia in 17 (total cholesterol (TC) > 5.18 mmol/l). Both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were increased, such that the mean TC/HDL-C and apolipoprotein B/apolipoprotein A1 (Apo B/Apo A1) ratios were below levels associated with increased coronary artery disease risk. Subjects with hypercholesterolemia did not differ from those with normal cholesterol values in current age or age at transplant, serum creatinine, serum albumin, serum triglycerides, HDL-C, TC/HDL-C ratio, Apo B/Apo A1 ratio, prednisone dose, body mass index, gender, use of thiazides or beta blockers, or family history of premature atherosclerosis. Coronary risk factors appear to cluster in these patients, with hypertension in 53% of those with hypercholesterolemia. Lipid profiles were not different in patients treated with prednisone-azathioprine vs. prednisone-azathioprine-cyclosporine A immunosuppression. A significant correlation was found between prednisone dose (mg/m2) and TC, LDL-C and TC/HDL-C. According to National Cholesterol Education Program guidelines, 32% of these long-term survivors of pediatric renal transplantation warrant at least dietary intervention and 10% are candidates for treatment with lipid-lowering drugs. This proportion is likely to increase as the safety of lipid-lowering agents is established in younger children.

Overall mortality was low (3.5%) in 199 children who received 217 transplants and quadruple immunosuppression. Graft survival was better in patients on quadruple immunosuppression, compared with historical patients on standard immunosuppression. When censored for deaths with a functioning graft, cumulative graft survival beyond one year was significantly better in patients on quadruple immunosuppression. Acute rejection was more common in CAD recipients and in retransplant recipients. Acute rejection was also more common in patients with FSGS, compared with other causes of ESRD. Preemptive transplants were not associated with a higher incidence of acute rejection. Late acute rejection episodes tended to be associated with a CsA dose < 5 mg/kg/day at one-year posttransplant. Chronic rejection was the major cause of graft loss. Risk factors for graft loss within the first posttransplant year were acute tubular necrosis and an initial CsA dose of < 5 mg/kg/day. Risk factors for graft loss after the first posttransplant year were late onset of the first acute rejection episode and a panel reactivity of > 25% at the time of transplant.

Transplantation began at the University of Minnesota in 1963. Treatment of diabetes and its complications has been emphasized since 1966, when the first pancreas-kidney transplant was done. Of 3,640 kidneys transplanted by 1992, 1,373 were for diabetic recipients, including 658 from living donors and 715 from cadaver donors. The results progressively improved; since 1984, survival rates of kidney grafts have been similar for diabetic and nondiabetic recipients, with three fourths of the grafts functioning at 4 years. As of 1992, 501 pancreas transplants had been done, including 170 simultaneous with a kidney, 142 after a kidney, and 188 alone for nonuremic diabetic patients; again, the results have improved: by the 1990s, graft survival rates were similar in the 3 recipient categories. Successful pancreas transplants have been shown by our coworkers to stabilize or improve neuropathy and prevent recurrence of diabetic nephropathy in kidney grafts. In an attempt to simplify endocrine replacement therapy, we have done 63 human islet transplants, 34 as allografts for patients with type I diabetes and 29 as autografts after total pancreatectomy to treat chronic pancreatitis. Insulin independence occurs for about 50% of islet autograft recipients. Two recent islet allograft recipients treated with 15-deoxyspergualin have had sustained insulin independence. We anticipate that endocrine replacement therapy by transplantation will become routine for diabetic patients as methods to prevent rejection are refined.

Renal transplantation for infantile cystinosis corrects renal failure and prolongs survival. However, after transplantation, the disease may develop in the allograft and continue to progress in nonrenal organs. We studied seven children (6 boys, 1 girl) with infantile cystinosis who received 11 renal transplants (3 cadaver, 8 living-related) between May 1969 and December 1986. The age at transplant ranged from 6 to 12 years (mean, 9.1 years). Four children received second renal transplants at a mean age of 17 years (range, 16 to 22 years). The mean period of follow-up was 138 +/- 47 months. Three children received cysteamine therapy prior to transplantation. Nonrenal complications of infantile cystinosis present before transplantation were photophobia (n = 3), corneal crystals (n = 5), hypothyroidism (n = 1), rickets (n = 6), and short stature (n = 7). Graft and patient survival did not differ from controls matched for the time of transplantation. Two patients died (1 pneumococcal sepsis, 1 respiratory failure due to pulmonary fibrosis) with functioning grafts 5 and 14 years posttransplant. Complications that developed posttransplant included photophobia (n = 1), corneal crystals (n = 2), hypothyroidism (n = 4), polyneuropathy (n = 1), pulmonary fibrosis (n = 1), abnormal electroencephalogram without clinical seizures (n = 1), bladder stones (n = 1), and diabetes mellitus (n = 2). One patient received a corneal transplant. All seven children failed to show improvement in growth following transplantation. Cystine crystals are present in graft-infiltrating cells, but do not seem to affect kidney allograft function.(ABSTRACT TRUNCATED AT 250 WORDS)

The treatment of choice for end-stage renal failure within the first year of life is controversial. Between September 1970 and February 1991, we performed 28 kidney transplants (27 primary, 1 retransplant, 23 living donor, 5 cadaver) in infants less than 1 yr of age (mean, 7 +/- 2 months; range, 6 wk to 12 months). The 1-yr patient survival rate for living donor recipients was 100% versus 20% for cadaver recipients (P = 0.0001). The 1-yr graft survival rate for living donor recipients was 96% versus 20% for cadaver recipients (P = 0.001). The 1-yr patient survival rate for cyclosporin A (CSA) recipients (N = 12) was 100% versus 75% for non-CSA recipients (P = 0.03). The 1-yr graft survival rate for CSA recipients was 92% versus 75% for non-CSA recipients (P = 0.08). There was no difference in the number of rejection episodes or serum creatinine levels in CSA versus non-CSA recipients. Compared with pretransplant values, the mean posttransplant standard deviation scores (SDS) for height (N = 18), weight (N = 22), and head circumference (N = 8) improved: height SDS from -1.9 to -1.5 (not significant); weight SDS from -2.5 to 0.6 (P less than 0.0005); head circumference SDS from -2.0 to -0.7 (P = 0.01). Because no other renal replacement therapy can match these results, we conclude that renal transplantation is the treatment of choice for infants with end-stage renal failure.

With current immunosuppressive protocols, 1- and 6-year graft survival is similar in diabetic and nondiabetic kidney transplant recipients. Living-donor transplant recipients have significantly better outcome. Death with function and chronic rejection remain the 2 predominant causes of graft loss for diabetic recipients. Compared with national statistics on diabetic patient survival on dialysis, our data suggest that transplantation is the treatment of choice for diabetic patients with end-stage renal disease.

Medicare uses a fixed reimbursement schedule to pay the initial hospital costs for renal transplantation. This creates the potential to underpay for patients who develop the common complication of delayed graft function. We undertook a pilot study to determine if delayed graft function resulted in higher hospital charges and thus a loss in revenue when caring for these patients. Of 34 patients who experienced delayed graft function between October 12, 1987 and July 7, 1989, 9 (group 1) were randomly selected for study. During this same period 136 patients had immediate graft function; from them, another 9 (group 2) were selected by matching age, sex, and date of transplantation. The average (+/- SD) hospital stays for groups 1 and 2 were 17 +/- 8 and 10 +/- 2 days, respectively (p less than 0.001). The average time on dialysis for group 1 was 10.3 +/- 6.3 days (range 2-22 days). All dollars values were adjusted to a 1989 level, and we excluded kidney acquisition costs and professional fees. The average per patient charges for group 1 were $41,474 +/- 15,211 (range $21,926-$66,311), compared with $23,774 +/- 3245 (range $19,317-$29,702) for group 2 (p less than 0.001). We adjusted the charge values to estimate actual costs by using our hospital's average cost:charge ratio of 0.90 for 1987 and 1988, and 0.85 for 1989; the group 1 and group 2 average patient costs were $37,157 +/- 13,836 and $21,397 +/- 2921, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1. The experience of 3,183 transplants between June 7, 1963 and September 30, 1990 at the University of Minnesota was reviewed. 2. Patients were divided into 4 historical periods-each era was associated with improved outcome. 3. As results have improved, the proportion of patients less than 5 years old and the proportion greater than 50 years old have increased. Type I diabetes has become the most common cause of renal failure in patients transplanted here. 4. The most important variable leading to improved outcome was donor source. Both HLA-identical and HLA-nonidentical LRD transplants have better outcome than CAD transplants (p less than 0.0001). 5. Multivariate analyses were done to determine risk factors for survival: a) in the first year, and b) in subsequent years. In the first year, age greater than 50, diabetes, and retransplantation had an adverse affect whereas LRDs and CsA immunosuppression were beneficial. Similar factors affected survival after the first year. HLA mismatch had no impact. 6. When death with graft function was excluded, diabetes and age greater than 50 were no longer risk factors, suggesting that the excess graft loss in these groups was due to patient death. 7. Chronic rejection and death with function remain the predominant causes of graft loss. 8. As protocols have evolved, results have improved, and previously "high-risk" patients are being successfully transplanted. Future efforts should be directed at decreasing graft loss from rejection and death with function.

Renal failure developed in 20 patients following blunt civilian trauma. Ten recovered normal renal function; 8 currently survive. Survivors and nonsurvivors did not differ in age, time from trauma to anuria, mean blood urea nitrogen or creatinine level prior to the first or to subsequent dialyses. However, there was an increased incidence of sepsis and liver failure in those who died. When outcome was related to site of injury, patients with closed head injury and/or intra-abdominal injury had a worse prognosis than those with thoracic or extremity injury only. Only 2 patients with perforated bowel survived; both had peritoneal dialysis combined with peritoneal lavage with antibiotic solutions. Mortality in patients with posttraumatic renal failure remains high; however, death is usually a result of associated complications rather than a result of the renal failure. Aggressive management of other complications of the trauma, especially sepsis or potential sepsis, is necessary. We recommend peritoneal dialysis combined with peritoneal antibiotic lavage where there is a potential for posttraumatic intra-abdominal sepsis associated with renal failure.

1. There have been 1,426 renal transplants performed at the University of Minnesota from January 1, 1980 through August 31, 1988. CsA+P was used by 260 adult recipients, CsA+P+AZA(+ALG) by 536. 2. In general, there are no significant differences in actuarial graft or patient survival rates between the 2 CsA protocols. This is true for all adults, for all adult CAD recipients, and for a matched control group of adult CAD recipients. 3. Cox's proportional hazards regression model also indicates that there is no significant difference between the 2 CsA regimens. Donor type, number of transplants, and age at transplant influence graft survival in all adult recipients. The use of LRD is still indicated in the CsA era. Diabetic status, age at transplant, and number of transplants affect patient survival. The model fits the observed data quite well. 4. Actuarial analysis and Cox regression failed to document a beneficial effect of HLA-A, B, and DR matching in patients receiving either CsA protocol. Our data do not support the HLA matching point system currently used by UNOS or the Terasaki proposal to give points based on mismatching. 5. A matched control analysis of adult CAD recipients indicates that CsA+P+AZA+ALG has alleviated the problems of our CsA+P protocol without lowering the graft and patient survival rates. Thus, the sequential therapy group has equivalent graft and patient survival rates but shorter duration of ATN, lower serum creatinine levels at 1 year, and fewer patients who require modifications of protocol. Sequential therapy is our treatment of choice.