Prolonged immunosuppression does not improve risk of sensitization or likelihood of retransplantation after kidney transplant graft failure.

The optimum approach towards immunosuppression withdrawal following kidney transplant failure is unclear. Prolonged weaning may be associated with reduced sensitization, less graft nephrectomy and greater likelihood of retransplantation, but conversely increased risk of infection, malignancy and death. We conducted a single-centre retrospective analysis of patients experiencing graft failure between 2007 and 2017, comparing rates of sensitization, retransplantation, nephrectomy, infection, malignancy and death between patients who had immunosuppression weaned over <90 vs. 90-180 vs. >180 days. Patient survival after immunosuppression withdrawal over <90 vs. 90-180 vs. >180 days was 73.3%, 72.1% and 80.4%, respectively (P = 0.35), with no differences in cPRA (80.06 vs. 81.21 vs. 85.42, P = 0.66) or retransplantation rate [24/31 (77.4%) vs. 21/35 (60.0%) vs. 22/36 (61.1%), P = 0.13]. There was significantly less nephrectomy after late immunosuppression cessation [10/42 (23.8%) vs. 7/42 (16.7%) vs. 3/43 (7.0%), P = 0.01] but no differences in infections or malignancy. On competing risk regression (death as competing risk) controlling for cofactors including age, nephrectomy and rejection, prolonged immunosuppression did not predict likelihood of retransplantation (SHR 1.000, P = 0.88). Prolonged immunosuppression withdrawal does not reduce sensitization or improve retransplantation rates but is associated with less nephrectomy. Immunosuppression withdrawal should be tailored to individual circumstances after graft failure.

A call-to-action for sustainability in dialysis in Brazil / Um apelo pela sustentabilidade na diálise no Brasil

ABSTRACT Human-induced climate change has been an increasing concern in recent years. Nephrology, especially in the dialysis setting, has significant negative environmental impact worldwide, as it uses large amounts of water and energy and generates thousands of tons of waste. While our activities make us responsible agents, there are also several opportunities to change the game, both individually and as a society. This call-to-action intends to raise awareness about environmentally sustainable practices in dialysis and encourages this important discussion in Brazil.

RESUMO A mudança climática induzida pela atividade humana tem sido foco de preocupações crescentes nos últimos anos. A nefrologia, particularmente a diálise, produz significativos impactos ambientais em todo o mundo em virtude da grande utilização de água e energia e da geração de milhares de toneladas de resíduos. Embora nossas atividades nos tornem agentes responsáveis, há várias oportunidades para mudar esse cenário, tanto individualmente como em sociedade. O presente artigo pretende ampliar a conscientização sobre práticas ambientalmente sustentáveis em diálise e estimular essa importante discussão no Brasil.

Predictive performance of different kidney function estimation equations in lung transplant patients.

BACKGROUND: There has been limited examination of the performance of glomerular filtration rate estimation (eGFR) equations in lung transplant populations. This study aimed to compare the performance of serum creatinine and cystatin C based eGFR equations with Tc-99m diethylenetriaminepentaacetic acid (DTPA) GFR measurements in individuals with end-stage lung disease, either prior to, or following, lung transplantation. METHODS: In this prospective observational study, participants underwent GFR measurements with Tc-99m Pentetate. Measured results were compared with GFR estimates derived from estimation equations [4-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C and creatinine-cystatin C combined equations]. RESULTS: Ninety-seven individuals were studied (77 post- and 20 wait-listed for transplantation). Median (range) radionucleotide GFR was 56.7ml/min/1.73m2 (22.8-109.2ml/min/1.73m2). In the study cohort as a whole, the CKD-EPI creatinine-cystatin C combined equation showed the highest performance, but was only slightly superior to the CKD-EPI creatinine equation. However, in individuals with cystic fibrosis, low arm muscle mass and/or low body mass index, all of the creatinine-based equations showed unacceptable performance. In these subgroups, improved GFR estimation was seen with the CKD-EPI cystatin C equation, and predictions were better still using the CKD-EPI creatinine-cystatin C combined equation. CONCLUSIONS: This study shows adequate predictive ability of CKD-EPI creatinine in the cohort as a whole, but unacceptable performance in patients with cystic fibrosis, low arm muscle mass and/or low body mass index. Our findings demonstrate that cystatin C may be a preferable filtration marker in these subgroups.

Specific rolling circle amplification of low-copy human polyomaviruses BKV, HPyV6, HPyV7, TSPyV, and STLPyV.

Eleven new human polyomaviruses have been recently discovered, yet for most of these viruses, little is known of their biology and clinical impact. Rolling circle amplification (RCA) is an ideal method for the amplification of the circular polyomavirus genome due to its high fidelity amplification of circular DNA. In this study, a modified RCA method was developed to selectively amplify a range of polyomavirus genomes. Initial evaluation showed a multiplexed temperature-graded reaction profile gave the best yield and sensitivity in amplifying BK polyomavirus in a background of human DNA, with up to 1 × 10(8)-fold increases in viral genomes from as little as 10 genome copies per reaction. Furthermore, the method proved to be more sensitive and provided a 200-fold greater yield than that of random hexamers based standard RCA. Application of the method to other novel human polyomaviruses showed successful amplification of TSPyV, HPyV6, HPyV7, and STLPyV from low-viral load positive clinical samples, with viral genome enrichment ranging from 1 × 10(8) up to 1 × 10(10). This directed RCA method can be applied to selectively amplify other low-copy polyomaviral genomes from a background of competing non-specific DNA, and is a useful tool in further research into the rapidly expanding Polyomaviridae family.

Genetics and nonmelanoma skin cancer in kidney transplant recipients.

Kidney transplant recipients (KTRs) have a 65- to 250-fold greater risk than the general population of developing nonmelanoma skin cancer. Immunosuppressive drugs combined with traditional risk factors such as UV radiation exposure are the main modifiable risk factors for skin cancer development in transplant recipients. Genetic variation affecting immunosuppressive drug pharmacokinetics and pharmacodynamics has been associated with other transplant complications and may contribute to differences in skin cancer rates between KTRs. Genetic polymorphisms in genes encoding the prednisolone receptor, GST enzyme, MC1R, MTHFR enzyme and COX-2 enzyme have been shown to increase the risk of nonmelanoma skin cancer in KTRs. Genetic association studies may improve our understanding of how genetic variation affects skin cancer risk and potentially guide immunosuppressive treatment and skin cancer screening in at risk individuals.

A differential impact of mycophenolic acid, prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients.

BACKGROUND: Soluble CD30 (sCD30) has been associated with rejection and graft loss in kidney transplantation, leading to the suggestion that sCD30 might be a useful biomarker to adjust immunosuppressant medication dosing. However, there has been minimal study of the influence of individual immunosuppressive drugs on sCD30 levels. AIM: To evaluate the influence of mycophenolic acid (MPA), prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients. METHODS: The sCD30 levels were measured pretransplant and 30 days posttransplant. Area under the concentration-time curve (AUC) for each drug was estimated on day 30 using validated, multiple regression-derived limited sampling strategies. RESULTS: One hundred twenty-five subjects were included. Median (interquartile range) sCD30 levels were lower on day 30 posttransplant compared with pretransplant [10.7 (3.7-20.1) pg/mL versus 66.5 (46.0-95.1) pg/mL; P < 0.0001]. On univariate analyses, day 30 sCD30 levels were negatively correlated with MPA exposure and positively correlated with tacrolimus exposure. Using multivariate logistic regression, higher tacrolimus exposure was independently associated with higher day 30 sCD30 levels (2.2 change in odds for an SD increase in tacrolimus AUC 0-12, P = 0.01; 5.5 change in odds for an SD increase in tacrolimus predose concentration, P < 0.0001). In contrast, MPA and total and free prednisolone exposures were not independently associated with sCD30 levels. CONCLUSIONS: The sCD30 levels are significantly reduced in the presence of combination immunosuppression but are differentially affected by different immunosuppressant agents. More research is required before introduction of sCD30 measurement into clinical practice can be considered.

NR1I2 polymorphisms are related to tacrolimus dose-adjusted exposure and BK viremia in adult kidney transplantation.

BACKGROUND: Pregnane X, encoded by the gene NR112, is a nuclear receptor whose primary role is to promote the detoxification and clearance of drugs and other foreign compounds from the body. AIM: The aim of this study was to analyze associations between NR1I2 polymorphisms, immunosuppressant drug exposure, and clinical outcomes in adult kidney transplant recipients. METHODS: Exposures to tacrolimus, mycophenolic acid, and total and free prednisolone were estimated at month 1 posttransplant using validated multiple regression-derived limited sampling strategies. RESULTS: In the 158 subjects studied, median (interquartile range) dose-adjusted exposure to tacrolimus was significantly higher in individuals carrying the NR1I2 8055T variant allele, when compared with exposure in wild-type individuals [20 (14, 22) µg·h/L/mg versus 15 (9, 24) µg·h/L/mg; P =0.0007]. Using multivariable logistic regression, NR1I2 8055T carrier status was independently predictive of higher dose-adjusted tacrolimus exposure (P=0.0005). Moreover, BK viremia was seen significantly more frequently in NR1I2 8055T allele carriers compared with wild-type individuals (38% vs 18%, P=0.005) and possession of the NR1I2 8055T allele imposed significantly higher odds of BK viremia (adjusted odds ratio, 2.76 [95% confidence interval, 1.33-7.73]; P=0.006). No significant difference in geometric mean peak BK viral replication titer was observed between 8055T carriers and noncarriers. No NR1I2 SNP or haplotype was significantly, independently associated with total or free prednisolone or MPA exposure. CONCLUSIONS: These data demonstrate an impact of pregnane X receptor polymorphisms on tacrolimus pharmacokinetics. Association of the 8055T allele with BK viremia suggests clinically significant "overimmunosuppression" in individuals with this genotype.

A randomized controlled trial of oral heme iron polypeptide versus oral iron supplementation for the treatment of anaemia in peritoneal dialysis patients: HEMATOCRIT trial.

BACKGROUND: Preliminary clinical evidence suggests that heme iron polypeptide (HIP) might represent a promising, novel oral iron supplementation strategy in chronic kidney disease. The aim of this multi-centre randomized controlled trial was to determine the ability of HIP administration to augment iron stores in darbepoetin (DPO)-treated patients compared with conventional oral iron supplementation. METHODS: Adult peritoneal dialysis (PD) patients treated with DPO were randomized 1:1 to receive two capsules daily of either HIP or ferrous sulphate per os for 6 months. The primary outcome measure was transferrin saturation (TSAT). Secondary outcomes comprised serum ferritin, haemoglobin, DPO dose and responsiveness, and adverse events. RESULTS: Sixty-two patients were randomized to HIP (n = 32) or ferrous sulphate (n = 30). On intention-to-treat analysis, the median (inter-quartile range) TSAT was 22% (16-29) in the HIP group compared with 20% (17-26) in controls (P = 0.65). HIP treatment was not significantly associated with TSAT at 6 months on multivariable analysis (P = 0.95). Similar results were found on per-protocol analysis and subgroup analysis in iron-deficient patients. Serum ferritin levels at 6 months were significantly lower in the HIP group (P = 0.003), while the cost of HIP was 7-fold higher than that of ferrous sulphate. No other differences in secondary outcomes were observed. CONCLUSIONS: HIP showed no clear safety or efficacy benefit in PD patients compared with conventional oral iron supplements. The reduction in serum ferritin levels and high costs associated with HIP therapy suggest that this agent is unlikely to have a significant role in iron supplementation in PD patients.

Pharmacogenetic influences on mycophenolate therapy.

Mycophenolic acid (MPA) is a cornerstone immunosuppressant therapy in solid organ transplantation. MPA is metabolized by uridine diphosphate glucuronosyltransferase to inactive 7-O-MPA-glucuronide (MPAG). At least three minor metabolites are also formed, including a pharmacologically active acyl-glucuronide. MPA and MPAG are subject to enterohepatic recirculation. Biliary excretion of MPA/MPAG involves several transporters, including organic anion transporting polypeptides and multidrug resistant protein-2 (MRP-2). MPA metabolites are also excreted via the kidney, at least in part by MRP-2. MPA exerts its immunosuppressive effect through the inhibition of inosine-5-monophosphate dehydrogenase. Several SNPs have been identified in the genes encoding for uridine diphosphate glucuronosyltransferase, organic anion transporting polypeptides, MRP-2 and inosine-5-monophosphate dehydrogenase. This article provides an extensive overview of the known effects of these SNPs on the pharmacokinetics and pharmacodynamics of MPA.

Polymicrobial peritonitis in peritoneal dialysis patients in Australia: predictors, treatment, and outcomes.

BACKGROUND: The study aim was to examine the frequency, predictors, treatment, and clinical outcomes of peritoneal dialysis-associated polymicrobial peritonitis. STUDY DESIGN: Observational cohort study using ANZDATA (The Australia and New Zealand Dialysis and Transplant Registry) data. SETTING & PARTICIPANTS: All Australian peritoneal dialysis patients between October 2003 and December 2006. PREDICTORS: Age, sex, race, body mass index, baseline renal function, late referral, kidney disease, smoking status, comorbidity, peritoneal permeability, center, state, organisms, and antibiotic regimen. OUTCOMES & MEASUREMENTS: Polymicrobial peritonitis occurrence, relapse, hospitalization, catheter removal, hemodialysis transfer, and death. RESULTS: 359 episodes of polymicrobial peritonitis occurred in 324 individuals, representing 10% of all peritonitis episodes during 6,002 patient-years. The organisms isolated included mixed Gram-positive and Gram-negative organisms (41%), pure Gram-negative organisms (22%), pure Gram-positive organisms (25%), and mixed bacteria and fungi (13%). There were no significant independent predictors of polymicrobial peritonitis except for the presence of chronic lung disease. Compared with single-organism infections, polymicrobial peritonitis was associated with higher rates of hospitalization (83% vs 68%; P < 0.001), catheter removal (43% vs 19%; P < 0.001), permanent hemodialysis transfer (38% vs 15%; P < 0.001), and death (4% vs 2%; P = 0.03). Isolation of fungus or Gram-negative bacteria was the primary predictor of adverse clinical outcomes. Pure Gram-positive peritonitis had the best clinical outcomes. Patients who had their catheters removed >1 week after polymicrobial peritonitis onset were significantly more likely to be permanently transferred to hemodialysis therapy than those who had earlier catheter removal (92% vs 81%; P = 0.05). LIMITATIONS: Limited covariate adjustment. Residual confounding and coding bias could not be excluded. CONCLUSIONS: Polymicrobial peritonitis can be treated successfully using antibiotics alone without catheter removal in most cases, particularly when only Gram-positive organisms are isolated. Isolation of Gram-negative bacteria (with or without Gram-positive bacteria) or fungi carries a worse prognosis and generally should be treated with early catheter removal and appropriate antimicrobial therapy.

Prevention of access-related infection in dialysis.

Access-related infections (ARIs), such as exit-site infections, tunnel infections, bacteremia, fungemia and peritonitis, are the Achilles' heel of dialysis, and contribute significantly to morbidity, mortality and excess healthcare costs in hemodialysis and peritoneal dialysis patient populations. Despite international guidelines recommending the avoidance of catheters for hemodialysis access, hospital admissions for vascular ARIs have doubled in the last decade. Moreover, repeated use of antibiotics to treat ARIs has been associated with the selection of multiresistant organisms, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. ARIs result from direct inoculation of skin organisms during access cannulation/connection, migration of skin organisms along dialysis catheters into the bloodstream or peritoneal cavity, or contamination and colonization of catheter lumens with subsequent biofilm formation. This paper will review the epidemiology, pathogenesis and prevention of ARIs. It will focus specifically on randomized, controlled trial evidence in relation to the safety and efficacy of aseptic techniques, nasal eradication of S. aureus, oral antimicrobial prophylaxis, topical antimicrobial prophylaxis (including disinfectants, antibiotics and antibacterial honey), antimicrobial catheter lock solutions (including gentamicin, citrate and ethanol), antimicrobial-impregnated catheters, catheter design (straight vs coiled, single vs double cuff), peritoneal dialysis catheter connectology, catheter insertion technique, germicidal devices, vaccines and preinsertion antibiotic prophylaxis.

The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with chronic kidney disease: a randomised controlled trial.

BACKGROUND: Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation. METHODS/DESIGN: This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m(2); aged >or=18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1beta, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study. DISCUSSION: To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12609000246280.

Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial).

BACKGROUND: The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet). METHODS: Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp(R), Amgen) for >or= 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control) or HIP (1 tablet twice daily) for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements) will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA). Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Key's index (DPO dosage divided by haemoglobin concentration), and occurrence of adverse events (especially gastrointestinal adverse events). DISCUSSION: This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry number ACTRN12609000432213.

A matched cohort pharmacoepidemiological analysis of steroid free immunosuppression in renal transplantation.

BACKGROUND: This longitudinal, sequential, matched closed-cohort design pharmacoepidemiological analysis examined the influence of maintenance steroid therapy in 380 first graft recipients after renal transplantation under conditions of normal clinical practice. METHODS: Nonexposed (steroid avoidance, n=190) and exposed (steroid treated, n=190) cohorts were matched 1:1 for key demographic factors, including donor source (living or deceased), diabetic status, panel reactive antibody level, recipient age (by decade), and sex. RESULTS: Cohorts were comparable for all variables except median human leukocyte antigen mismatch (4 vs. 3, P=0.03), use of tacrolimus (90.0% vs. 59.5%, P

A comparison of the predictive performance of different methods of kidney function estimation in a well-characterized HIV-infected population.

BACKGROUND: Glomerular filtration rate (GFR) estimation equations have never been validated in the HIV population. This pilot study aimed to compare all currently available methods of kidney function assessment with nuclear GFR in HIV-infected adults. METHODS: Patients underwent GFR measurement with (99m)Tc-diethylenetriaminepentaacetic acid (Tc-99m Pentetate), and measured values were compared with results of creatinine-based estimation equations [abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) formula and Cockcroft-Gault (CG) formulae], 24-hour urine creatinine clearance and estimated cystatin C GFR. RESULTS: Twenty-seven HIV-infected adults were studied. Most were male and Caucasian, with a mean age of 52 years. Median CD4 was 290 cells/mm(3), 70% of patients had HIV RNA <50 copies/ml and all were receiving highly active antiretroviral therapy (median 5 drugs). Median Tc-99m Pentetate-GFR was 91 ml/min/1.73 m(2). Despite greater bias and similar accuracy, the MDRD formula was more precise than the CG formula, regardless of whether CG estimations were corrected for ideal body weight or body surface area. Relative accuracy within 30% of nuclear GFR was greater for the MDRD formula than for all other methods. The performance of 24-hour urine creatinine clearance was similar to that of the MDRD formula for patients with GFR <90 ml/min/1.73 m(2), although it performed less well at higher GFR. The performance of cystatin C GFR was inferior to that of all the creatinine-based methods. CONCLUSIONS: While no method of kidney function estimation performed highly, both 24-hour urine creatinine clearance and the MDRD formula performed with a level of precision and accuracy sufficient for clinical decision making. Our findings support the preferential use of the MDRD formula in the treated HIV population and suggest that there are no HIV-specific factors that limit equation applicability. Larger validation studies are needed to confirm our findings and allow generalization to the HIV population at large.

Coronary artery calcification scores in patients with chronic kidney disease prior to dialysis: reliability as a trial outcome measure.

BACKGROUND: Coronary artery calcification (CAC) is prevalent in patients with chronic kidney disease (CKD). Data on the reliability and validity of high-resolution computerized tomography (HRCT) in patients with CKD is lacking. The purpose of this study was to evaluate the inter- and intra-reviewer agreement and inter-scan reproducibility of CACS measurement with HRCT in a cohort of patients with CKD prior to dialysis, and to compare the change in CACS at 30 minutes to the change in CACS over 1 year. METHODS: Thirty-three patients with CKD not yet on dialysis underwent an HRCT scan at baseline and 1 year to assess for CAC and CAC progression. Two radiologists independently reviewed films and each radiologist re-reviewed a randomly selected subset of films they had previously viewed, to assess for inter-reviewer and intra-reviewer reliability, respectively. Patients underwent a repeat scan within 30 min of the first baseline scan to assess for inter-scan reproducibility. RESULTS: At baseline, eight patients (24%) had no CAC. Of the 25 patients (76%) with CAC, 10 (40%) had severe calcification. Intra-reviewer agreement was 83%. Inter-reviewer agreement ranged between 77 and 94%. Six (27%) of the patients with >30 baseline CACS had >15% change in CACS following repositioning. Four of these patients had an increase in CACS with position change [18% (95% CI: 5-40%)]. Of the 21 patients who underwent a follow-up scan at 1 year, 7 (33%) demonstrated CACS progression. CONCLUSIONS: There is significant imprecision in HRCT-derived CACS in CKD patients. This suggests a need for standardization of methods of CACS measurement with HRCT.

Renal graft rejection after allogeneic peripheral-blood stem cell transplantation.

A 28-year-old woman underwent peripheral-blood stem cell transplantation from her HLA-identical sister for cytogenetic progression of Fanconi anemia. She had received a living-related renal allograft from her father 2 years previously. Nine days after peripheral-blood stem cell transplantation, she developed acute renal failure secondary to acute rejection. Severe microangiopathic hemolysis developed, and cyclosporine therapy was discontinued. Renal biopsy showed humoral rejection and thrombotic microangiopathy. Despite daily plasmapheresis and immunosuppression, she remained dialysis dependent. The renal graft was removed, with rapid resolution of microangiopathic hemolysis. At no stage was there evidence of acute graft-versus-host disease. We speculate that the engrafting third-party hematopoiesis produced acute renal allograft rejection with secondary microangiopathic hemolysis through a graft-versus-graft mechanism.