Progressive decline of function in renal allografts with normal 1-year biopsies: Gene expression studies fail to identify a classifier.

Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c-statistic = .59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and .58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e., those with a relatively normal 1-year biopsy and eGFR > 40) remains difficult.

Mayo Adhesive Probability (MAP) score of non-donated kidney aids in predicting post-operative renal function following donor nephrectomy.

BACKGROUND: To examine the association of preoperative Mayo Adhesive Probability (MAP) scores in the donor (MAPd) and non-donor kidneys (MAPnd) with post-donation renal function. METHODS: Three hundred thirty-one patients undergoing hand assisted laparoscopic donor nephrectomy (HALDN) were reviewed. MAPd and MAPnd were obtained. Estimated glomerular filtration rate (eGFR) was recorded preoperatively and at 1 day, 1 month, and 6 months postoperatively. RESULTS: Two hundred females and 131 males were evaluated with median BMI 26.4 kg/m2 (range 17.1-39.6) and median age 45 years (range 19-78). MAPd score was 0 for 231 patients (69.8%) and > 0 for 100 patients (30.2%). MAPnd score was 0 for 234 patients (70.7%) and > 0 for 97 patients (29.3%). The median preoperative eGFR was 86.6 ml/min/1.73m2 (range 48.8-138.4). After adjusting for preoperative eGFR, BMI, ASA score, and kidney sidedness, postoperative eGFR was associated with MAP score in the non-donated kidney (p = 0.014) but not in the donated kidney (p = 0.24). Compared to donors with MAPnd = 0, donors with a MAPnd > 0, mean eGFR was - 2.33 ml/min/1.73m2 lower at postoperative day 1 (95% CI - 4.24 to - 0.41, p = 0.018), - 3.02 ml/min/1.73m2 lower at 1 month (95% CI - 5.11 to - 0.93, p = 0.005), and - 2.63 ml/min/1.73m2 lower at 6 months postoperatively (95% CI - 5.01 to - 0.26, p = 0.030). CONCLUSIONS: MAP score > 0 in the non-donated kidney is associated with worse renal function in the 6 months following HALDN.

Kidney transplantation on extracorporeal life support for primary cardiac allograft dysfunction.

Patients undergoing heart-kidney transplants who have primary graft dysfunction (PGD) of the heart are at risk of losing both organs, which may cause reluctance on the part of the transplant team to proceed with transplanting the kidney while the transplanted heart is being supported by mechanical device. We describe a case series in which 2 patients received kidney transplants while on veno-arterial ECMO support for PGD after heart transplant. Both patients are alive more than 1 year following transplant, with good cardiac and renal function and no signs of cardiac rejection. Kidney transplant surgery is safe for patients on veno-arterial ECMO support for cardiac PGD. It allows the heart recipient to receive a kidney from the same donor with both immunologic and survival advantages.

Arterial Blood Pressure at Liver Transplant Evaluation Predicts Renal Histology in Candidates With Renal Dysfunction.

Renal dysfunction is common in liver transplantation (LT) candidates, but differentiating between reversible and irreversible renal injury can be difficult. Kidney biopsy might be helpful in differentiating reversible from irreversible renal injury, but it is associated with significant complications. We aimed to identify pre-LT predictors of potentially reversible renal injury using histological information obtained on pre-LT renal biopsy. Data on 128 LT candidates who underwent pre-LT kidney biopsy were retrospectively collected and correlated with renal histological findings. Indications for kidney biopsy were iothalamate glomerular filtration rate (iGFR) ≤40 mL/minute, proteinuria >500 mg/day, and/or hematuria. According to the biopsy diagnosis, patients were grouped into the following categories: normal (n = 13); acute tubular necrosis (ATN; n = 25); membranoproliferative glomerulonephritis (n = 19); minimal histological changes (n = 24); and advanced interstitial fibrosis (IF) and glomerulosclerosis (GS) (n = 47). Compared with patients having advanced IF/GS, patients with normal biopsies and those with ATN had lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) and higher international normalized ratio and total bilirubin levels (<0.05 for all). Both SBP and DBP directly correlated with the degree of IF and GS (R = 0.3, P ≤ 0.02 for all). SBP ≤90 mm Hg was 100% sensitive and 98% specific in correlating with normal biopsies or ATN, whereas SBP ≥140 mm Hg was 22% sensitive and 90% specific in correlating with advanced IF/GS. Model for End-Stage Liver Disease score, serum creatinine, iGFR, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis or degree of IF or GS. In conclusion, SBP at the time of LT evaluation correlates with renal histology, and it should be included along with other clinical and laboratory markers in the decision-making process to list patients with renal dysfunction for LT alone versus simultaneous liver-kidney transplantation.

Renal outcomes of liver transplant recipients who had pretransplant kidney biopsy.

BACKGROUND: Kidney biopsy has been recommended to guide kidney allocation in selected liver transplant (LT) candidates with renal dysfunction. However, post-LT-alone renal outcomes in recipients who showed evidence of reversible renal injury and limited chronicity on pre-LT kidney biopsy are unclear. METHODS: Renal outcomes of 41 LT recipients who had pre-LT kidney biopsy for unexplained renal dysfunction, proteinuria, and hematuria were retrospectively reviewed. All biopsies showed less than 30% interstitial fibrosis and less than 30% to 40% glomerulosclerosis. Study endpoints were renal replacement therapy (RRT) at 1 month and the need for kidney transplantation at 1 year from LT. RESULTS: Six patients were on RRT at time of biopsy. Median (range) iothalamate glomerular filtration rate and 24-hr urinary protein excretion for the remaining 35 patients were 29 (6-88) mL/min per 1.73 m(2) and 65 (0-4,338) mg/day, respectively. Glomerulonephritis and acute tubular necrosis were present in 28 (68%) and 16 (39%) of the cases. Six patients (15%) did not recover kidney function at 1 month and RRT at time of LT was the only factor associated with this endpoint (P=0.04). Seven of the 31 (22%) patients with 1-year data met criteria for kidney transplantation within the first post-LT year. Surgical re-exploration was the only factor associated with the need for kidney transplantation at 1 year (P=0.05). CONCLUSIONS: The most LT recipients with minimal chronic changes on pre-LT kidney biopsy recovered kidney function within 1 month from LT. A small but significant percentage met criteria for kidney transplantation at 1 year because of the development of unforeseen post-LT complications.

Impact of early conversion from tacrolimus to sirolimus on chronic allograft changes in kidney recipients on rapid steroid withdrawal.

BACKGROUND: Calcineurin-inhibitor therapy is a contributing factor to the origin of interstitial fibrosis and tubular atrophy (IFTA). METHODS: We conducted a prospective randomized trial of conversion of tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal. We compared the chronic changes (IFTA and sum of Banff chronic scores--Total Score) on protocol biopsies at 1 month, 1 year, and 2 years in all randomized patients. We compared the outcomes between treatment groups and analyzed the impact of previous rejection on the chronic changes. RESULTS: We randomized 122 patients, 62 to sirolimus and 60 to tacrolimus. The 1-year biopsy was performed in 54 patients (90%) of the tacrolimus group and 56 patients (90%) of the sirolimus group. The proportion of biopsies with IFTA more than or equal to 2 and the Total Score more than 2 increased over the 2 years but were not different between the study groups at any time point. On the 1-year biopsy, there was more IFTA, and the fraction with Total Score more than 2 was higher in the tacrolimus group with previous rejection. In the cohort without rejection, there was a significant progression of the IFTA and Total Score between 1 and 2 years in both the sirolimus and tacrolimus groups. CONCLUSION: Conversion from tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal does not decrease the progression of chronic changes on protocol biopsies during the first 2 years even in those patients without previous acute rejection.