Dennis Mishler

Hyporesponsiveness to erythropoietin: causes and management.

In patients with chronic kidney disease, erythropoietin resistance is common, costly, and has implications beyond the management of anemia because the presence of erythropoietin resistance portends mortal outcomes. Exploring the provenance of erythropoietin resistance may be facilitated by the consideration of the pathogenetic triad of iron-restricted erythropoiesis, inflammation, and bone marrow suppression. Challenging to diagnose because of difficulty in interpreting tests of iron deficiency, iron-restricted erythropoiesis should be considered in patients who require high doses of erythropoietin, have low transferrin saturation (eg, <20%-25%), and do not have very high ferritin (eg, <1,200 ng/mL); a therapeutic trial of intravenous iron may be worthwhile. Aluminum intoxication is a rare cause of iron-restricted erythropoiesis that may manifest as microcytic hypochromic anemia. A decrease in serum albumin concentration may signal the presence of inflammation, which may be manifest (such as because of a recent illness or infection) or occult; the latter include clotted synthetic angioaccess, failed renal allograft, dialysis catheter, periodontal disease, underlying malignancy, or uremia per se. Marrow hyporesponsiveness may be improved by increasing the delivered dialysis dose, using ultrapure dialysate, maintaining adequate vitamin B12 and folate stores, or by treating hyperparathyroidism. In summary, improving the outcomes of erythropoietin-resistant patients will require complete patient assessment that goes beyond considerations of iron and erythropoietin dose alone. Given that erythropoietin dose is associated with mortality, mitigating erythropoietin resistance has the potential to improve patient outcomes.

The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.

Mujtaba MA, Goggins W, Lobashevsky A, Sharfuddin AA, Yaqub MS, Mishler DP, Brahmi Z, Higgins N, Milgrom MM, Diez A, Taber T. The strength of donor‐specific antibody is a more reliable predictor of antibody‐mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.
Clin Transplant 2011: 25: E96–E102.

Risk factors for native kidney dysfunction in patients with abdominal multivisceral/small bowel transplantation

Kidney dysfunction is a recognized complication after non‐renal solid organ transplantation, particularly after intestinal transplant. In our study, we reviewed data on 33 multivisceral transplant (MVT)‐ and 15 isolated small bowel (ISB)‐transplant patients to determine risk factors for kidney dysfunction. Kidney function was estimated by modified diet in renal disease (MDRD) and Schwartz formula for adults and children, respectively. Acute kidney injury (AKI) was defined as an increase in the serum Cr (sCr) greater than twofold. Kidney function declined significantly at one yr after transplantation with 46% of subjects showing an estimated GFR (eGFR) <60 mL/min. Patients with an episode of AKI were more likely to have reduced eGFR than those without AKI (p < 0.025). In linear regression analyses, age, pre‐transplant sCr, eGFR at postoperative day (POD) 30, 90, 180, 270, and tacrolimus level at POD 7 showed significant correlation with one yr post‐transplant eGFR (p < 0.05). Pediatric patients and patients with MVT had lesser decline in kidney function compared with adults or patients with ISB. In conclusion, risk factors for post‐transplant kidney dysfunction in intestinal transplantation included age, pre‐transplant sCr, AKI episode, eGFR at POD 30, 90, 180, 270, and tacrolimus level at POD 7.

BK virus nephropathy in simultaneous pancreas kidney transplant: A potentially preventable cause of kidney allograft loss

More than half of the simultaneous pancreas kidney transplant (SPK) patients afflicted with BK virus nephropathy (BKVN) lose their kidney allograft. Fear of pancreatic rejection limits the ability to reduce immunosuppression; this may result in inadequate treatment of BKVN.

Correlation between CT-based measured renal volumes and nuclear-renography-based split renal function in living kidney donors. Clinical diagnostic utility and practice patterns

Living donor evaluation involves imaging to determine the choice of kidney for nephrectomy. Our aim was to study the diagnostic accuracy and correlation between CT‐based volume measurements and split renal function (SRF) as measured by nuclear renography in potential living donors and its impact on kidney selection decision.

Early findings of prospective anti-HLA donor specific antibodies monitoring study in pancreas transplantation: Indiana University Health Experience

The significance of donor‐specific antibodies (DSA) is not well known in the setting of pancreas transplantation. Since December 2009, we prospectively followed pancreas transplant patients with single‐antigen‐luminex‐bead testing at one, two, three, six, and then every six months for the first two yr. Thirty‐five of the 92 patients that underwent pancreas transplantation (13 pancreas‐alone [PTA], 20 with a kidney [SPK], and two after a kidney [PAK]) agreed to participate in study. Median age at transplant was 45 yr and follow‐up was 23 months. Majority were Caucasian (n = 33) and male (n = 18). Rabbit anti‐thymocyte globulin induction was used. Median HLA‐mismatch was 4.2 ± 1.1. Eight patients (7SPK, 1PAK) developed post‐transplant DSA at median follow‐up of 76 d (26–119), 1 SPK had pre‐formed DSA. Seven patients had both class I and class II DSA, one with class I and one with class II only. Mean peak class I DSA‐MFI was 3529 (±1456); class II DSA‐MFI was 5734 (±3204) whereas cumulative DSA MFI (CI + CII) was 9264 (±4233). No difference was observed in the patient and donor demographics among patients with and without DSA. One patient in non‐DSA group developed acute cellular rejection of pancreas. From our data it appears that post‐transplant DSA in pancreas allograft recipients may not impact the early‐pancreatic allograft outcomes. The utility of prospective DSA monitoring in pancreatic transplant patients needs further evaluation and long‐term follow‐up.

Pre-transplant angiotensin receptor II type 1 antibodies and risk of post-transplant focal segmental glomerulosclerosis recurrence

Post‐kidney transplant recurrence of focal segmental glomerulosclerosis (FSGS) is a major problem. AT1R is expressed on podocyte; its expression is elevated in the proteinuric state. Using an ELISA, we tested pre‐transplant sera of 28 patients with history of idiopathic FSGS for anti‐AT1R levels and serum soluble urokinase‐type plasminogen activator receptor (suPAR) as a biomarker for risk of recurrence of FSGS. Sera from 11 patients with polycystic kidney disease (PKD) were used as controls. Twelve patients had biopsy proven post‐transplant FSGS recurrence at 1.5 months. No difference was found in the pre‐transplant suPAR levels of FSGS patients (5993 ± 2292 pg/mL) vs. PKD (7334 ± 4538 pg/mL) (p = 0.23). Serum suPAR levels in patients with FSGS recurrence (5786 ± 1899 pg/mL) vs. no FSGS recurrence (6149 ± 2598 pg/mL) (p = 0.69) were not different. Anti‐AT1R levels in patients with FSGS were 12.66 ± 11.85 U/mL vs. 8.69 ± 6.52 U/mL in PKD (p = 0.32); however, a difference was found in patients with and without FSGS recurrence 20.41 ± 14.36 U/mL 6.84 ± 4.181 U/mL, respectively (p < 0.01). Area under curve for suPAR and anti‐AT1R to predict post‐transplant FSGS recurrence was 0.51 and 0.84, respectively. Pre‐transplant anti‐AT1R levels appear to be a helpful biomarker in identifying patients at high risk of post‐transplant FSGS recurrence.

Long-term outcomes of transplant recipients referred for angiography for suspected transplant renal artery stenosis

Our aim was to study the long‐term outcomes of all transplant recipients who underwent angiography for suspected TRAS at our institution. The patients were divided into TRAS+ve and TRAS−ve groups based upon angiographically confirmed results. TRAS was confirmed in 58.1% of 74 patients with median time of 8.9 months. Primary angioplasty alone was performed in 56% of patients with TRAS, while the remaining had PTA with stent (PTAS). There was reduction in systolic and diastolic BP (165 ± 19–136 ± 15 mmHg and 82 ± 14 mmHg to 68 ± 12 mmHg; p < 0.05) and number of antihypertensive drugs (3.5 ± 0.9–2.7 ± 1.0; p < 0.05). Overall, graft survival and patient survival from time of transplant were similar in both groups. Graft function was similar for the patients with treated TRAS+ve as compared to TRAS−ve over time. Graft survival and patient survival when compared to an age‐ and year of transplant‐matched cohort control group were also similar. In conclusion, angiography for suspected TRAS is more likely to yield a confirmatory result early in the transplant course as compared to late. Treatment of TRAS in these patients had sustained long‐term graft function. Alternative etiologies of HTN and graft dysfunction should be sought for recipients further out from transplant.

Early fatal cutaneous lower extremity angiosarcoma associated with deep venous thrombosis in a renal transplant recipient

Angiosarcomas are extremely rare malignant tumors of vascular origin. We describe a 63-year-old recipient after a kidney transplant who had an angiosarcoma in the lower extremity that presented after new-onset deep venous thrombosis and was not associated with any fistula. There was rapid progression to metastasis and death. We reviewed the literature of this rare malignant tumor in kidney transplant patients.

Re-transplants compared to primary kidney transplants recipients: A mate kidney paired analysis of the OPTN/UNOS database

Outcomes of kidney re‐transplant recipients (RTR) were compared to primary recipients (FTR) from paired donor kidneys. Organ Procurement and Transplantation Network (OPTN) database was used to identify deceased donors (n = 6266) who donated one kidney to an RTR and the mate kidney to an FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs. 52 yr, p < 0.001) and had higher proportion of plasma reactive antibody >80 (25% vs 7%, p < 0.001). There were higher 0 mismatches in RTR (19% vs. 16%, p < 0.001). There were more pre‐emptive transplants in RTR (24% vs. 21%, p = 0.002). Delayed graft function (28% vs. 25%, p = 0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at one, three, and five yr (95.7%, 90.2%, and 82.5% vs. 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at one, three, and five yr (91.1%, 82.4%, and 70.9% vs. 87.8%, 77.4%, and 66.1% p < 0.001). Death‐censored allograft survival rates were higher in FTR group at one, three, and five yr (91.3%, 82.7% and 71.4% vs. 88%, 77.7% and 66.5% p < 0.001). In todays era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors.