Terminal Creatinine Research Articles

Risk Factors and Outcome of Delayed Graft Function after Cadaveric Kidney Transplantation: A Report from the Thai Transplant Registry

Introduction Kidney transplantation is the best treatment for end-stage renal disease patients. Delayed graft function (DGF) remains one of the major problems after cadaveric kidney transplantation. This study has reported the risk factors and outcomes of DGF using data from Thai Transplant Registry Database. Methods The data of all cadaveric kidney transplantations (CD-KT) were retrieved from the database. DGF was defined as a failure to decrease the serum creatinine within 72 hours or a requirement for dialysis within the first week after transplantation. We performed logistic regression analysis to correlate donor features (age, sex, cardio-pulmonary resuscitation (CPR), brain death from a cerebrovascular accident (CVA), best and last serum creatinine) with recipient demographics (age, sex) and clinical outcomes cold ischemic time [CIT] and DGF. Results We analyzed 756 CD-KT including 320 (42%) patients experiencing DGF. Upon multivariate analysis, factors significantly correlated with DGF were CIT ( P < .001), donor last serum creatinine ( P < .001), interleukin 2 monoclonal antibody induction ( P = .004), donor age ( P = .017), donor CVA ( P = .012), and prior peritoneal dialysis (PD) ( P = .012). There was no significant correlation between DGF and donor height, weight, sex, CPR, brain death from CVA, best serum creatinine, recipient age, or sex in multivariate analysis. Graft survivals at 1 and 5 years after transplantation were significantly lower among the DGF group namely, 91.0% vs. 95.2% and 78.7% vs. 86.0%, respectively ( P = .006). Patient survival was also significantly lower 94.1% vs. 96.4% and 82.1% vs. 92.2%, respectively, ( P = .001). Conclusion A higher value of the donor's terminal serum creatinine, CIT, IL2mAb induction, PD prior to KT and donor age increased the risk for DGF after CD-KT. DGF significantly lowered kidney allograft and patient survivals at 1 and 5 years after transplantation among the Thai population.

Results of Kidney Transplantation from High–Terminal Creatinine Donors and the Role of Time-Zero Biopsy

Background Deceased-donor kidney transplantation (DDKT) from high–terminal creatinine donors is associated with lower graft survival. These kidneys may be considered for discarding, worsening the organ shortage crisis. Using time-zero biopsy for histologic evaluation of these kidneys, we identified those organs eligible for transplantation, seeking to achieve better graft utility with comparable outcomes. Methods From April 2004 to April 2008, 55 patients underwent DDKT. A time-zero biopsy was used to examine glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriolar narrowing. A scoring system was used to determine a discard. Results Twenty-five patients received DDKT from donors whose terminal creatinine levels were >2.0 mg/dL (high terminal creatinine, HTC group) and 30 from donors whose terminal creatinine levels were <2.0 mg/dL (low terminal creatinine, LTC group). Patients who accepted kidneys from HTC donors had shorter waiting times ( P = .011) but a higher incidence of delayed graft function after transplantation ( P < .001). Nonetheless, 5-year graft survival rates were similar between the two groups. Conclusions With a time-zero biopsy for histologic evaluation, kidneys recovered from high–terminal creatinine donors can be transplanted to overcome the organ shortage while achieving reasonable graft survival.

The Risk Factors of Delayed Graft Function and Comparison of Clinical Outcomes After Deceased Donor Kidney Transplantation: Single-Center Study

IntroductionThe aim of this study was to analyze risk factors for delayed graft function (DGF) after deceased donor kidney transplantation and to compare the clinical outcomes of non-DGF versus DGF recipients. Patients and methodsFrom January 2004 to June 2008, 75/154 kidneys were transplanted into 74 recipients. We classified the recipients into two groups: group 1 (n = 61) without DGF and group 2 (n = 13) with DGF. ResultsOn univariate analysis, recipient age (P = .048) cause of brain death (traumatic brain injury vs disease, P = .016), blood urea nitrogen (P = .002), serum creatinine (P = .001), arterial pH (P = .019), and serum sodium level (P = .012) just before organ procurement showed significant differences. On multivariate analysis, the cause of brain death (P = .015, hazard ratio [HR]: 7.086), the terminal serum creatinine ≥1.5 mg/dL before organ procurement (P = .007, HR: 10.132), and recipient age over ≥50 years (P = .021, HR: 7.767) were independent risk factors for the development of DGF. Graft failures occurred among 5/74 recipients with 5-year graft survivals between group 1 and group 2 of 91.7% and 84.6%, respectively. Patient death occurred in five cases, most by due to infection. The 5-year patient survival between groups 1 and 2 were 93.9% and 84.6%, respectively (P = .106). ConclusionThe independent risk factors for DGF were the cause of brain death, the terminal creatinine level, and the recipient age. In deceased donor kidney transplantation, DGF may have less effect on long-term patient and graft survivals.

Machine Perfusion Preservation for Kidney Grafts With a High Creatinine From Uncontrolled Donation After Cardiac Death

Background This study evaluated the usefulness of machine perfusion preservation parameters as selection criteria for donation after cardiac arrest (DCD) with high creatinine level. The aim of this study is to evaluate to whether DCD donor >50 years old and with high creatinine are acceptable. Methods We examined 17 kidneys from uncontrolled DCD who showed creatinine levels >3.0 mg/dL before procurement. The study included the following two groups: group 1 ( n = 9), donor age <50 years old versus group 2 ( n = 8), donor age >50 years old. Results There were no significant differences in donors or preservation conditions among the 2 groups, including age, terminal creatinine, warm ischemic time, cold perfusion time, and total ischemic time. A greater resistance of 47.9 mmHg/mL per min/g was observed among group 2, compared with 42.5 mmHg/mL per min/g in group 1. A shorter ATN period (8.2 days) was noted in group 1, compared with 21.2 days for group 2. The flow rate (mL/g/min) was not significantly different between the two groups. The best-Cr level was 1.22 mg/dL in group 1 and 1.94 mg/dL in group 2. Conclusion Machine perfusion flow was a reliable indicator of graft viability in uncontrolled DCD, particularly kidneys with high creatinine level. Even older donors were acceptable if the machine perfusion preservation parameters such as flow rate and pressure were acceptable; however, they may show severe delayed graft function.

Single center experience transplanting kidneys from deceased donors with terminal acute renal failure

Transplantation of kidneys from deceased donors with terminal acute renal failure (ARF) is uncommon. We reviewed retrospectively our single-center experience with transplantation of ARF donor kidneys. From January 2007 through September 2008, we transplanted 25 kidneys from 17 ARF donors; 22 kidneys were from standard criteria donors. Mean donor age was 34 years. Mean admission and terminal donor serum creatinine values were 1.3 mg/dL and 3.1 mg/dL. All but 2 kidneys were placed on pump preservation; mean cold ischemia time was 27 hours. The recipient group had a mean age of 49 years and a mean waiting time of 24 months. Patient and graft survival rates were 100% and 92%, respectively, with a mean follow-up of 12 months. Delayed graft function occurred in 8 patients (32%), mean initial duration of stay was 6 days, 3 patients (12%) required re-operation, 3 patients (12%) had acute rejection, and 8 patients (32%) developed infections. Mean 1- and 12-month recipient serum creatinine and glomerular filtration rate values were 1.9 mg/dl (45 mL/min) and 1.5 mg/dl (50 mL/min), respectively. Kidneys from deceased donors with terminal ARF have excellent short-term outcomes and represent another potential method to safely expand the donor pool.

The Alphabet Soup of Kidney Transplantation

There is significant variability in the quality of deceased-donor kidneys that are used for transplantation. The quality of the donor kidney has a direct effect on important clinical outcomes such as acute rejection, delayed graft function, and patient and allograft survival. Expanded-criteria donors (ECDs) refer to older kidney donors (> or =60 yr) or donors who are aged 50 to 59 yr and have two of the following three features: Hypertension, terminal serum creatinine >1.5 mg/dl, or death from cerebrovascular accident. By definition, ECD kidneys have a 70% greater likelihood of failure compared with one from a 35-yr-old male donor who died from a motor vehicle accident. Donation after cardiac death (DCD) is a small but rapidly growing fraction of donors. An ECD kidney transplant recipient has a projected average added-life-years of 5.1 yr compared with 10 yr for a kidney recipient from a standard-criteria donor. Kidney transplantation from DCD seems to have similar allograft and patient survival compared with kidney from donation after brain death; however DCD transplantation has a 42 to 51% risk for delayed graft function (need for at least one dialysis treatment during the first week after transplantation) compared with 24% in an standard-criteria donor kidney transplant. Familiarity with the comprehensive allocation rules governing different categories of deceased-donor kidneys by the nephrologists and dialysis team providers is essential to maximizing patient autonomy and to improve the outcomes of kidney transplantation.

Outcomes and Utilization of Kidneys from Deceased Donors with Acute Kidney Injury

Utilization and long-term outcomes of kidneys from donors with elevated terminal serum creatinine (sCr) levels have not been reported. Using data from the Scientific Registry of Transplant Recipients from 1995 to 2007, recipient outcomes of kidneys from adult donors were evaluated stratified by standard criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and by sCr </=1.5, 1.6-2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained. The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6-2.0 and >2.0 mg/dL, compared to </=1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr. Of potential SCDs, the adjusted risk of discard was higher with sCr >2.0 mg/dL (adjusted odds ratio [AOR] 7.04, 95% confidence interval [CI] 6.5-7.6) and 1.6-2.0 mg/dL (AOR 2.7; CI 2.5-2.9) relative to sCr </=1.5 mg/dL. Among potential SCDs, elevated terminal creatinine is a strong independent risk factor for kidney discard; yet, when kidney transplantation is performed elevated donor terminal creatinine is not a risk factor for graft loss. Further research is needed to identify safe practices for the optimal utilization of SCD kidneys from donors with acute kidney injury.

Role of Pulsatile Perfusion With Tissue Plasminogen Activator in Deceased Donor Kidneys With Extensive Glomerular Thrombosis

Background Pulsatile perfusion (PP) improves delayed graft function, whereas tissue plasminogen activator (tPA) lyses thrombi. We studied the role of PP with tPA containing perfusate in deceased donor kidneys (DDK) with 50% thrombosed glomeruli. Methods Fourteen DDK with extensive glomerular thrombi on biopsies were preserved using PP with histidine-tryptophan-ketoglutarate solution containing tPA. Wedge biopsies were repeated after PP. Results Causes of donor death included closed head trauma in 8, anoxia in 2, and stroke in 4. Donors who averaged 33.3 years old displayed a final 24-hour urine volume of 1933 mL, a terminal serum creatinine level of 1.8 mg/dL, a blood urea nitrogen of 20 mg/dL, and a platelet count of 128,000/μL. The initial flow of 47 mL improved to 111 mL/min after 16.17 hours of perfusion. Resistive indices (RI) decreased from 0.69 to 0.26 at 4.2°C. Biopsy specimens after PP showed a reduction in glomerular thrombi from 50% to 23%. Recipients averaged 54.9 years old. Cold ischemia time averaged 35.5 hours. One patient displayed primary allograft nonfunction, 3 required transient dialysis, and 10 showed prompt allograft function. Recipient follow-up averaged 12 months, with serum creatinine levels of 4.3 mg/dL at 1 week, 2.0 mg/dL at 1 month, and 1.6 mg/dL at last follow-up. Conclusions Renal allografts with extensive glomerular thrombosis improved their biopsy appearance following PP with tPA. Improvement in PP parameters allowed successful transplantation of such kidneys that otherwise would have been discarded. PP with tPA appears to be beneficial for kidneys with extensive glomerular thrombosis.

A Systematic Review of Kidney Transplantation From Expanded Criteria Donors

During the past few years, there has been renewed interest in the use of expanded criteria donors (ECD) for kidney transplantation to increase the numbers of deceased donor kidneys available. More kidney transplants would result in shorter waiting times and limit the morbidity and mortality associated with long-term dialysis therapy. Systematic review of the literature. Kidney transplantation population. Studies were identified by using a comprehensive search through MEDLINE and EMBASE databases. Inclusion criteria were case series, cohort studies, and randomized controlled trials assessing kidney transplantation in adult recipients using ECDs. A special focus was given to studies comparing the evolution of kidney transplantation between standard criteria donors (defined as a donor who does not meet criteria for donation after cardiac death or ECD) and ECDs (defined as any brain-dead donor aged > 60 years or a donor aged > 50 years with 2 of the following conditions: history of hypertension, terminal serum creatinine level >or= 1.5 mg/dL, or death resulting from a cerebrovascular accident). Criteria used to define and select ECDs, practice patterns, long-term outcomes, early complications, and some patient issues, such as selection criteria and immunosuppressive management. ECD kidneys have worse long-term survival than standard criteria donor kidneys. The optimal ECD kidney for donation depends on adequate glomerular filtration rate and acceptable donor kidney histological characteristics, albeit the usefulness of biopsy is debated. This review is based mainly on data from observational studies, and varying amounts of bias could be present. We did not attempt to quantitatively analyze the effect of ECD kidneys on kidney transplantation because of the huge heterogeneity found in study designs and definitions of ECD. Based on the available evidence, we conclude that patients younger than 40 years or scheduled for kidney retransplantation should not receive an ECD kidney. Patients 40 years or older, especially with diabetic nephropathy or nondiabetic disease, but a long expected waiting time for kidney transplantation, show better survival receiving an ECD kidney than remaining on dialysis therapy.

Cold Pulsatile Perfusion of Pediatric Kidney Allografts

Kidney transplantation from small pediatric donors is increasingly being used as a means to optimize the organ supply (1); however, transplantation of small pediatric kidneys from unstable or donation after cardiac death (DCD) donors is rarely performed. Although pulsatile perfusion (PP) is being used to evaluate the viability of marginal or DCD adult donor organs (2) only one report of its application to pediatric kidneys has been published (3). The underutilization of PP in small pediatric kidneys is probably because of concerns of mechanical injury to the pediatric kidney vasculature that has an already established increased risk of thrombosis. We describe the use of PP to test the viability of small pediatric kidneys from a category four DCD donor. The donor, a 2-year-old boy, was in a drowning accident and required cardiopulmonary resuscitation for 35 min before arrival to the hospital. The terminal creatinine was 0.8 mg/dL. During transfer to the operating room for organ recovery the donor became unstable and vital signs were nondetectable. The patient was quickly prepped and draped and the aorta rapidly cannulated. Approximately 20 min had passed between loss of vital signs and organ perfusion with preservation solution. The left ureter was injured near the hilum during the aortic cannulation because of difficulty of exposure from scar tissue related to a prior gastroschisis repair. The right kidney was intact. Because of concerns about the instability of the donor before recovery, PP was performed to test the viability of the right kidney. The kidneys were perfused en bloc by the technical staff of The University of Florida Medical Center at 4°C to 6°C with 1 L of Belzer Machine Perfusion Solution (Organ Recovery Systems, Des Plaines, IL) on an RM3 organ PP machine (Waters Medical Instruments, Rochester, MN) at 60 bmp. The suprarenal aorta was clamped and the infrarenal aorta was cannulated with a 6F aortic cannula (Waters) (Fig. 1). The perfusion pressure was initially set at 40/32 mm Hg and resulted in a perfusion flow of 30 mL/min and resistance of 0.89 mm Hg/mL/min. Two hours later the flow and resistance was 71 mL/min and 0.37 mm Hg/mL/min, respectively (pressure 38/30 mm Hg). Perfusion flow and resistance did not improve after additional time of PP. These kidneys met our acceptance criteria (resistance ≤0.40 mm Hg/mL/min) for adult kidneys undergoing PP.FIGURE 1.: Pulsatile perfusion of en bloc pediatric kidneys.After ligation of the left hilum and discard of the left kidney, transplantation was performed in a 38-year-old man (weight 62 kg) by anastomosing the donor infrarenal aorta and vena cava to the recipient external iliac artery and vein, respectively, with continuous 6-0 nonabsorbable suture. The cold ischemia time was 22 hr. The kidney functioned immediately. At 6 months posttransplantation the recipient creatinine is 1.5 mg/dL. According to the Organ Procurement and Transplant Network data 93 kidneys from donors younger than 2 years have been evaluated with machine perfusion between 1994 and 2007 (accessed April 15, 2008). To our knowledge there is one published report describing PP of pediatric kidneys. In 1978 Munda et al. (2) performed PP in 12 en bloc kidneys from donors 6 days to 8 years of age. The mean perfusion pressure for the en bloc kidneys was 57/27 mm Hg. Flow rates were similar to adult values. Pulsatile perfusion is being used to evaluate the viability of marginal or DCD adult donor organs (3). Pulsatile perfusion of small pediatric kidneys is feasible and should be considered as an option to test the viability of kidneys when the donor is unstable or DCD. Future studies are needed to determine acceptable perfusion resistances in pediatric subgroups. Ivan Zendejas Maximilian Polyak Liise K. Kayler Division of Transplantation and Hepatobiliary Surgery Department of Surgery University of Florida College of Medicine Gainesville, FL

Can Machine Perfusion Decrease the Likelihood of Discard Among Biopsied Kidneys?

Many factors, such as donor risk factors and renal function, have been shown to be associated with an increased likelihood of discard after recovering kidneys from deceased donors. When these factors are insufficient for assessment, renal biopsy is often performed at the time of harvest to assess suitability. Our aims were to identify factors that predict the discard of a biopsied kidney and to assess the impact of machine perfusion (MP) on kidney discard. We biopsied 678 kidneys from deceased donors aged ≥40 years from 2001 to 2006. We used a logistic regression model to estimate the adjusted odds ratios for kidney discard. Thirty-nine percent (n = 261) of biopsied kidneys were discarded. Kidneys with glomerulosclerosis (GS) > 20% had the highest likelihood of discard. Other significant predictors of discard included extreme donor age, final resistance (>40), atherosclerosis, interstitial fibrosis, arteriolosclerosis, and terminal serum creatinine value (SCr) > 1.5 mg/dL. MP kidneys (n = 69) were less likely to be discarded than cold storage (CS) kidneys after adjusting for other factors (adjusted odds ratio = .13, P < .001). In conclusion, abnormal biopsy findings were associated with the highest likelihood of discard. MP was used in only 10% of the cases; however, the use of MP was associated with a decreased likelihood of discard among biopsied kidneys.

Nephron number determines susceptibility to renal mass reduction-induced CKD in Lewis and Fisher 344 rats: implications for development of experimentally induced chronic allograft nephropathy

The Fisher 344 (F344) rat kidney transplanted to a Lewis rat recipient is a common model of chronic renal allograft nephropathy (CAN); however, CAN does not develop when the Lewis kidney is grafted into a F344 recipient. In this study we investigated whether a difference in nephron number/glomerular volume exists between the strains that could contribute to a greater susceptibility to development of kidney disease in the F344. Separate animals, male F344 and Lewis rats, were subjected to either sham surgery or right uni-nephrectomy and infarction of 2/3 of the left kidney, to produce a 5/6 ablation/infarction injury (5/6 A/I). Serial urinary protein excretions were measured, a terminal 24-h creatinine clearance was obtained and rats were killed 11 weeks after surgery and kidneys were harvested for pathology. Glomerular volumes were measured in the sham controls of each strain. Glomerular number was counted in separate, normal rats of each strain. The normal F344 had approximately 30% fewer glomeruli than Lewis rats that were larger in volume. The sham F344 had similar creatinine clearance and glomerular structure to the Lewis shams, although BP and urine protein excretion were higher. After 5/6 A/I the F344 developed more severe proteinuria and structural kidney damage. When factored for kidney weight, the F344 rats exhibited a greater compensatory hyperfiltration in response to 5/6 A/I, compared to Lewis. The F344 strain is more vulnerable to development of progressive kidney damage due to 5/6 A/I, compared to the Lewis. This is likely due to the lower nephron number/greater glomerular volume of the F344 that may also account for the greater susceptibility to CAN exhibited by this strain.

Outcomes After Transplantation of Deceased-Donor Kidneys with Rising Serum Creatinine

The increasing number of candidates for kidney transplantation and relatively unchanged deceased-donor pool has led to expansion in the criteria for donor acceptability. Outcomes of kidneys from donors with progressively rising creatinine values have not been reported. Patients transplanted between September 2003 and August 2006 with kidneys from donors with peak creatinine levels >2.0 mg/dL were stratified into two groups based on the terminal creatinine and evaluated for outcome: (1) falling creatinine (FC)(n= 27), terminal creatinine at least 0.2mg/dL less than peak, and (2) rising creatinine (RC)(n=24), terminal creatinine = peak. The mean terminal creatinine was significantly higher in the RC group (3.2 +/- 1.3 mg/dL) compared to the FC group (1.9 +/- 0.9 mg/dL)(p<0.0001). Peak creatinine values were similar (RC, 3.2 +/- 1.3; FC, 3.1 +/- 1.3; p=0.6521) between the two groups. Rates of delayed graft function (RC, 24%; FC 32%; p=0.7881) and mean creatinine at follow-up (RC, 1.6 +/- 0.6, FC 1.6 +/- 0.4; p=0.3533) were not significantly different. With a mean follow-up of 287 +/- 274 days, allograft survival was 92% in the RC recipients and 89% in the FC recipients. Under certain conditions, kidneys from donors with rising serum creatinine can be used safely with reasonable early outcomes.

Transplantation of Dual Adult Kidneys Into a Recipient With Minimal Abdominal Vascular Access

Dual kidney transplantation has become increasingly utilized as a means of decreasing the organ shortage and optimizing outcomes of marginal kidneys (1). Among deceased-donor kidney transplant recipients at the University of Pittsburgh Medical Center, transplantation of dual kidneys transplants from adult donors has increased from 4% (7/04–6/05), to 11% (7/05–6/06), to 32% since 7/06. Our criteria to perform dual renal transplantation generally includes donor age ≥70 years, or younger donors with glomerulosclerosis ≥10%, and/or arterial luminal narrowing of 25% to 50%. Recipients of dual kidneys must have adequate space for the transplantation of two kidneys (either both kidneys in one iliac fossa or single bilateral kidneys), so that candidates are usually limited to those who have had one or no previous kidney transplants. We describe the transplantation of dual adult kidneys into a recipient with two previous kidney transplants (one on each side) and diffuse severe aortoiliac atherosclerosis. Two kidneys from a 68-year-old male donor who expired from a myocardial infarction were accepted as an open offer with permission to utilize as a two-for-one transplantation. The terminal creatinine and calculated CCr were 1.7 mg/dL and 70 mL/min, respectively. Kidney biopsy showed glomerulosclerosis in 14% (9/63) and 5% (3/59) of the glomeruli of each kidney, respectively, and minimal interstitial fibrosis, arteriosclerosis, and arteriolosclerosis. Pulsatile perfusion of the kidneys demonstrated terminal resistances of 30% and 32%. Three wait-listed candidates were >50 years of age. The first patient, a 55-year-old male with end-stage renal disease secondary to hypertension with two failed kidney transplants and historically high antibody levels (100% class I and II enzyme-linked immunosorbent assays), had a history of several previously positive crossmatches. He shared five human leukocyte antigen antigens with this donor. To optimize his chances of transplantation, he was included in the crossmatch and it was negative for both T and B cells. The recipient operation was performed through a midline incision with the intention of revascularizing the kidneys separately to the common iliac vessels; however, the patient had diffuse hard aortoiliac atherosclerotic disease. Attempts to isolate the distal left external iliac vessels were aborted, because the previous kidney transplant was too large to allow room for exposure. The right iliac fossa was more optimal as the previous kidney transplant was atrophic. With retraction of the ilioinguinal ligament, 4 cm segments of recipient external iliac artery and vein were isolated and were healthy enough to allow anastomosis of a segment of donor common iliac artery (Y-graft) and vein (from a different donor with a compatible blood type), respectively. The right kidney renal artery and vein were anastomosed to the internal iliac artery of the Y-graft end-to-end and the middle portion of the common iliac vein graft end-to-side. The left kidney was next revascularized by end-to-end anastomoses to the external iliac artery and vein grafts, respectively (Fig. 1. The ureters were anastomosed to the bladder using separate extravesical ureteroneocystostomies over 6F 12 cm double-J stents. The cold ischemia was 21 hr. The renal allografts functioned immediately; the creatinine is currently 1.7 at 2 months follow-up.FIGURE 1.: Iliac vessel Y-graft to dual kidney allografts.The technique described illustrates a method to transplant dual adult kidneys in recipients with suboptimal vascular access for transplantation. Liise K. Kayler Ron Shapiro Department of Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Ernesto Molmenti Department of Surgery University of Arizona Tucson, Arizona

Microscopic Intrarenal Particles After Pulsatile Machine Preservation Do Not Adversely Affect Outcomes After Renal Transplantation

Introduction Our center has recently observed foreign carbohydrate-appearing particles (FP) on transplant postreperfusion biopsy specimens: (PRBx). Methods To further characterize FPs, we reviewed all renal transplant RBx (30–45 minutes) performed between September 1, 2004 and December 3, 2005. Donor, preservation, and outcome variables were collected among patients with FP. Results A total of 135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]). Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United States) with Belzer MP solution (Trans Med, Elk River, Minn, United States). Donor age was 39.8 ± 15.7 years. Terminal creatinine level was 1.45 ± 0.8 mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold ischemia time was 28.8 ± 9.1 hours with 14.3 ± 5.1 hours of MP. In 13 of 15 patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35). Characteristics of FP Particles were 10–30 μ and globular in shape. FP were not visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff–(PAS) positive and were refractile under polarized light. FP were seen segmentally within glomerular capillaries in all cases and in peritubular capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had a biopsy within the first week with no identifiable FP. Outcomes Recipient age was 45.3 ± 11.6 years. Eight patients (53.3%) had delayed graft function. Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine level was 1.59 ± 0.35 mg/dL. One graft was lost to early thrombosis in a patient with a hypercoagulable state and 1 patient died of sepsis at 2 months. All remaining 13 patients are alive with excellent graft function at a median follow-up of 6.7 months (range, 3–17 months). Conclusions Microscopic intrarenal particles may be seen on DD kidney PRBx after MP. These FPs likely originate from surgical gloves. FPs are too small to be captured by standard filters but clear spontaneously and do not have deleterious effects on renal function or outcomes.

Osmotic nephrosis in a renal transplant recipient

CASE PRESENTATION A 59-year-old Hispanic male with a history of type II diabetes mellitus, hypertension, and end-stage renal disease (on hemodialysis for 2 years) was called in for a kidney transplant. He was in his usual health, having received dialysis earlier in the day. The kidney donor was from an expanded criteria pool and was a 59-year-old Caucasian male with diabetes mellitus who expired following a cerebrovascular accident. He had a terminal creatinine of 1.3mg/dl (114.92 μmol/l (nl range 0.6-1.2 mg/dl/53.04-106.08 μmol/l)) and no evidence of proteinuria. A donor renal biopsy revealed 10-15% tubular atrophy and interstitial fibrosis. There was a six-antigen mismatch, and cold ischemia time was 31 h. The final complement-dependent cytotoxic and flow cytometry crossmatch were negative. Renal transplantation was performed. At the time of transplantation, the patient received alemtuzumab (Campath; anti-CD52 monoclonal antibody) and solumedrol as induction therapy. The patient had an intra-operative episode of hypotension that resolved with a 500 ml bolus of normal saline and 250 ml of 6% hetastarch lactate electrolyte solution. At the completion of surgery, the patient was stable and was extubated and moved to recovery. On physical exam, he was normotensive with normal sinus rhythm, clear lungs, good dorsalis pedis pulses, and no peripheral edema. He had been anuric before surgery, but had made 10 ml of urine during the first hour. One hour after surgery, the patient's systolic blood pressure dropped to 80 mmHg. In an effort to sustain his blood pressure, he was given multiple boluses of normal saline, lactate Ringers solution, and an additional 11 of 6% hetastarch. He was eventually started on vasopressin and moved to the Intensive Care Unit. His hematocrit remained stable, but his potassium was elevated at 6.0 mM/I. Continuous renal replacement therapy was initiated. Renal ultrasound initially was unable to demonstrate arterial or venous blood flow. After 4 h, his blood pressure improved and he was weaned off vasopressin. A repeat ultrasound 24 h later showed restoration of arterial and venous blood flow. Maintenance immunosuppression was started on post-operative day 1 and included tacrolimus and mycophenolate mofetil. His tacrolimus trough level ranged between 9 and 13 ng/ml. The patient remained oliguric and hemodialysis-dependent during the first week. Due to delayed graft function and a creatinine of 6.2 mg/dl (548.08 μmol/l), renal allograft biopsy was performed on post-operative day 8.

Validation of a nomogram for predicting the likelihood of delayed graft function in Australian adult deceased donor renal transplant recipients

To the Editor, Delayed graft function (DGF), defined as the need for dialysis within 72 h of renal transplantation where the graft subsequently functions, is associated with significant morbidity, including an increased risk of acute allograft rejection, prolonged patient hospitalization, increased health-care costs and poorer graft survival.1–3 Pretransplantation prediction of the likelihood of DGF would therefore be extremely useful for informing patient and organ management decisions. Recently, a nomogram for predicting DGF was developed in the USA, based on United States Renal Data System (USRDS) data extracted from 13 846 adult deceased donor renal transplants performed between 1996 and 1999.4 To date, this nomogram has not been validated in an independent cohort and has not been evaluated outside the USA, where the incidence of DGF (23.7%) is higher than in other countries (e.g. Australia 15%).5 We retrospectively applied the US nomogram to 598 deceased donor renal transplants performed at the Princess Alexandra Hospital between 1994 and 2004 (89% Caucasian, 61% male, recipient age 44.6 ± 14.3 years, donor age 36.4 ± 16.3 years, cold ischaemic time 13.6 ± 4.8 h). Calculation of DGF scores was based on recipient factors (male +7, pretransplant diabetes mellitus +5, HLA mismatches ×1.925, panel reactive antibodies ×0.175, previous transfusions +4, previous transplants +10, pretransplant dialysis +58, no pretransplant dialysis +18, single-organ transplant plus pretransplant dialysis +20) and donor factors (age [years − 13]×5, anoxia +5, cerebrovascular accident +4, hypertension +7, non-beating-heart donor +29, cold ischaemic time hours ×1, terminal serum creatinine concentration µmol/L ×0.065). The overall rate of DGF in the study population was 5.9%, which was much lower than that of the USRDS training sample (23.7%). Higher DGF nomogram scores were associated with a higher risk of DGF (<110, 0%; 110–129, 1.8%; 130–139, 3.4%; 140–149, 10.9%; =150, 17.9%). A cut-off score of 140 was associated with a sensitivity of 74% and a specificity of 71%. The area under the receiver operator characteristic curve was 0.76 (Fig. 1), which compared favourably with the USRDS training sample (0.71). Receiver operator characteristic curve for the application of the delayed graft function nomogram to 598 deceased donor renal transplants performed at the Princess Alexandra Hospital between 1994 and 2004. In conclusion, the USRDS nomogram performed well in the population in the present study despite a very low rate of DGF. Thus, the nomogram may have more universal applicability beyond the initial US study group in predicting DGF and may improve pretransplantation clinical decision making.

The use of expanded criteria donor organs for transplantation

Expanded criteria donors (ECD) of kidneys include all those aged ≥60 years and donors aged 50–59 years with at least 2 of the following 3 medical criteria: (1) cerebrovascular accident as the cause of death, (2) terminal serum creatinine concentration >1.5 mg/dL, and (3) history of systemic hypertension. ECD kidneys now account for 20% of all deceased donor kidneys in the United States, with the fraction being as high as 35% in some donation service areas. However, procured ECD kidneys continue to be discarded at a significantly higher rate (41%) compared with 8% for non-ECD kidneys. Patients who elect to be offered and receive ECD kidneys have survival benefits of decreased long-term mortality between 17% and 27% when compared to waiting longer and subsequently receiving an standard criteria donors organ, but only if the waiting time is more than 44 months. The experience with ECD kidneys in the United States suggests that organ donation and transplantation rates can be significantly improved through the systematic incorporation of ECD policies into organ procurement and transplantation schemes. More refined definition of ECD and rigorous assessment of the outcomes of ECD organ transplantation will further contribute to improving the use of all donated organs.

Expanded Criteria Donors: Process and Outcomes

Expanded criteria donor (ECD) kidneys are transplantable deceased donor (DD) kidneys for which the average patient, graft survival, and renal function are inferior when compared to standard criteria DD kidneys. Although the term ECD kidneys has been used since the early 1990s to describe kidneys with various characteristics associated with poorer outcomes, the concept has been formally implemented in U.S. organ allocation. A DD kidney is considered to be an ECD organ if the estimated adjusted risk of graft failure is > or = 70% (RR > or = 1.70) compared to DD kidneys with standard characteristics of transplant suitability. The donor characteristics that define an ECD kidney include age > or = 60 years, or age 50-59 years plus two of the following: cerebrovascular accident as the cause of death, preexisting hypertension, or terminal serum creatinine greater than 1.5 mg/dl. In the aggregate, recipients of ECD kidneys have improved survival compared to end-stage renal disease (ESRD) patients on the kidney transplant waiting list. Patient survival is 5% lower at 1 year and 8-12% lower at 3-5 years for ECD kidney recipients. Adjusted graft survival in ECD kidneys is 8% lower at 1 year and 15-20% lower at 3-5 years after transplantation compared to standard criteria donor kidneys. However, patients less than 40 years of age, African Americans, Asians for whom the median waiting time is less than 1350 days receive no survival benefit from ECD kidney transplantation. Informed choice by the potential recipient is a prominent feature of the allocation policy regarding ECD kidneys. Since there are recipient characteristics associated with no survival benefit following ECD transplantation, nephrologists who refer patients for kidney transplantation should be familiar with the combination of donor and recipient factors that are likely to yield detrimental results.

Excellent Outcomes after Transplantation of Deceased Donor Kidneys with High Terminal Creatinine and Mild Pathologic Lesions

Outcomes after kidney transplantation using deceased donors with high terminal creatinine are not well described but potentially represent an underutilized source of renal allografts. Utility of renal biopsy of these kidneys is similarly not well established. To better understand the posttransplant function of kidneys from donors with high terminal creatinine, we reviewed our database of almost 500 cadaveric kidney transplants. We compared the 65 nonexpanded criteria donors with a final donor creatinine > or = 2.0 mg/dl (range 2.0-4.9 mg/dl) with kidneys procured from donors with terminal creatinine of <1.5. Biopsy results were correlated with graft function. Kidneys from deceased donors with high terminal creatinine performed as well as kidneys from donors with a normal terminal creatinine with respect to primary non-function, acute rejection, 6-year graft and patient survival, and function over the first 48 months. High creatinine kidneys with moderate or severe lesions on biopsy demonstrated poorer function at 6 months and 1 year as compared to those with mild or no histological lesions. Under select conditions, kidneys from donors with high terminal creatinine can be used safely with excellent results.