Utilization and clinical outcomes of kidney transplants from deceased donors with albuminuria in the UK: a national cohort study.

BACKGROUND: Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilization, survival and function. METHODS: We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥2+ on dipstick testing, on kidney utilization, early graft function, graft failure and estimated glomerular filtration rate (eGFR). RESULTS: Eighteen percent (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% versus 82%; odds ratio 0.70, 95% confidence interval 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (hazard ratio 0.91, 95% confidence interval 0.74 to 1.11). There was also no association with delayed graft function, patient survival or eGFR at 1 or 3 years. CONCLUSIONS: Our study suggests reluctance in the UK to utilize kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilization without negatively impacting transplant outcomes.

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study.

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7-14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.

The effect of initiation of renin-angiotensin system inhibitors on haemoglobin: A national cohort study.

AIMS: To determine whether initiation of treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARBs) is associated with a subsequent reduction in haemoglobin in the general population. METHODS: We undertook a national cohort study over a 13-year period (2004-2016), using routine primary healthcare data from the UK Clinical Practice Research Datalink. We compared ACEI/ARB initiation with calcium channel blocker (CCB) initiation, to minimise confounding by indication. We included all first ACEI/ARB or CCB prescriptions in adults with at least 1 haemoglobin result in the 12 months before and 6 months after drug initiation. Our primary outcome was a ≥1 g/dL haemoglobin reduction in the 6 months after drug initiation. RESULTS: We examined 146 610 drug initiation events in 136 655 patients. Haemoglobin fell by ≥1 g/dL after drug initiation in 19.5% (16 936/86 652) of ACEI/ARB initiators and 15.9% (9521/59 958) of CCB initiators. The adjusted odds ratio of a ≥1 g/dL haemoglobin reduction in ACEI/ARB initiators vs CCB initiators was 1.15 (95% confidence interval 1.12-1.19). CONCLUSION: ACEI/ARBs are associated with a modest increase in the risk of a haemoglobin reduction. For every 100 patients in our study that initiated a CCB, 16 experienced a ≥1 g/dL haemoglobin decline. If the effect is causal, 3 additional patients would have experienced this outcome if they had received an ACEI/ARB. This may have implications for drug choice and monitoring for many patients in primary care. Further research could identify patients at higher risk of this outcome, who may benefit from closer monitoring.

Donor-Transmitted Cancer in Orthotopic Solid Organ Transplant Recipients: A Systematic Review.

Donor-transmitted cancer (DTC) has major implications for the affected patient as well as other recipients of organs from the same donor. Unlike heterotopic transplant recipients, there may be limited treatment options for orthotopic transplant recipients with DTC. We systematically reviewed the evidence on DTC in orthotopic solid organ transplant recipients (SOTRs). We searched MEDLINE, EMBASE, PubMed, Scopus, and Web of Science in January 2020. We included cases where the outcome was reported and excluded donor-derived cancers. We assessed study quality using published checklists. Our domains of interest were presentation, time to diagnosis, cancer extent, management, and survival. There were 73 DTC cases in liver (n = 51), heart (n = 10), lung (n = 10) and multi-organ (n = 2) recipients from 58 publications. Study quality was variable. Median time to diagnosis was 8 months; 42% were widespread at diagnosis. Of 13 cases that underwent re-transplantation, three tumours recurred. Mortality was 75%; median survival 7 months. Survival was worst in transmitted melanoma and central nervous system tumours. The prognosis of DTC in orthotopic SOTRs is poor. Although re-transplantation offers the best chance of cure, some tumours still recur. Publication bias and clinical heterogeneity limit the available evidence. From our findings, we suggest refinements to clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020165001, Prospero Registration Number: CRD42020165001.

Measurement of Muscle Strength in Haemodialysis Patients by Pinch and Hand Grip Strength and Comparison to Lean Body Mass Measured by Multifrequency Bio-Electrical Impedance.

BACKGROUND: Muscle weakness is a risk factor for mortality in haemodialysis (HD) patients; we wished to determine whether measuring the composition of the arm with bioimpedance was associated with arm muscle strength. METHODS: We measured pinch strength (PS) and hand grip strength (HGS) in 250 adult HD patients with corresponding post-dialysis multifrequency bioelectrical assessments with segmental body analysis. RESULTS: Mean age 64.0 ± 15.6, 66% male and 45.6% diabetic. The maximum HGS in the dominant or non-fistula arm was 18.9 ± 9.2 kg and PS 4.09 ± 1.96 kg respectively, with a correlation of r = 0.80, p < 0.001. HGS was associated with body cell mass (ß 0.37, p < 0.001) and PS with appendicular muscle mass (ß 0.06, p < 0.001). Both HGS and PS were independently associated with the ratio of extracellular water (ECW) to total body water (TBW); ß -139.5, p = 0.024, ß -44.8, p < 0.001 in the arm. The presence of an arterio-venous fistula increased the ECW/TBW ratio in the arm from 0.383 ± 0.009 to 0.390 ± 0.012, p < 0.05. CONCLUSION: Muscle strength measured by HGS and PS was associated with both markers of whole body and segmental body composition within the arm, particularly ECW/TBW. Bioimpedance measurements and assessment of muscle strength should be measured in the non-fistula arm.

Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission.

Importance: Cancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate their organs, opinions vary on the risks involved. Objective: To determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival. Design, Setting, and Participants: This was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022. Exposures: A history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes. Main Outcomes and Measures: Transmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history. Results: This study included a total of 282 donors (median [IQR] age, 42 [33-54] years; 154 females [55%]) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls. Conclusions and Relevance: Results of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group.

Solid Organ Transplantation From Deceased Donors With Infective Endocarditis: The UK Experience.

BACKGROUND: There is little evidence regarding the use of organs from deceased donors with infective endocarditis. We performed a retrospective analysis of the utilization, safety, and long-term survival of transplants from donors with infective endocarditis in the United Kingdom. METHODS: We studied deceased donor transplants over an 18-y period (2001-2018) using data from the UK Transplant Registry. We estimated the risk of infection transmission, defined as a microbiological isolate in the recipient matching the causative organism in the donor in the first 30 days posttransplant. We examined all-cause allograft failure up to 5 years in kidney and liver recipients, comparing transplants from donors with endocarditis with randomly selected matched control transplants. RESULTS: We studied 88 transplants from 42 donors with infective endocarditis. We found no cases of infection transmission. There was no difference in allograft failure between transplants from donors with infective endocarditis and matched control transplants, among either kidney (hazard ratio, 1.48; 95% CI, 0.66-3.34) or liver (hazard ratio, 1.14; 95% CI, 0.54-2.41) recipients. Compared with matched controls, donors with infective endocarditis donated fewer organs (2.3 versus 3.2 organs per donor; P < 0.001) and were less likely to become kidney donors (odds ratio, 0.29; 95% CI, 0.16-0.55). CONCLUSIONS: We found acceptable safety and long-term allograft survival in transplants from selected donors with infective endocarditis in the United Kingdom. This may have implications for donor selection and organ utilization.

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

BACKGROUND: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. METHODS: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. RESULTS: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. CONCLUSIONS: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

Utilization and Outcomes of Single and Dual Kidney Transplants from Older Deceased Donors in the United Kingdom.

BACKGROUND AND OBJECTIVES: Kidneys from elderly deceased donors are often discarded after procurement if the expected outcomes from single kidney transplantation are considered unacceptable. An alternative is to consider them for dual kidney transplantation. We aimed to examine the utilization of kidneys from donors aged ≥60 years in the United Kingdom and compare clinical outcomes of dual versus single kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the United Kingdom Transplant Registry from 2005 to 2017 were analyzed. We examined utilization rates of kidneys retrieved from deceased donors aged ≥60 years, and 5-year patient and death-censored graft survival of recipients of dual and single kidney transplants. Secondary outcomes included eGFR. Multivariable analyses and propensity score analysis were used to correct for differences between the groups. RESULTS: During the study period, 7841 kidneys were procured from deceased donors aged ≥60 years, of which 1338 (17%) were discarded; 356 dual and 5032 single kidneys were transplanted. Donors of dual transplants were older (median, 73 versus 66 years; P<0.001) and had higher United States Kidney Donor Risk Indices (2.48 versus 1.98; P<0.001). Recipients of dual transplants were also older (64 versus 61 years; P<0.001) and had less favorable human leukocyte antigen matching (P<0.001). After adjusting for confounders, dual and single transplants had similar 5-year graft survival (hazard ratio, 0.81; 95% CI, 0.59 to 1.12). No difference in patient survival was demonstrated. Similar findings were observed in a matched cohort with a propensity score analysis method. Median 12-month eGFR was significantly higher in the dual kidney transplant group (40 versus 36 ml/min per 1.73 m2; P<0.001). CONCLUSIONS: Recipients of kidneys from donors aged ≥60 years have similar 5-year graft survival and better graft function at 12 months with dual compared with single deceased donor kidney transplants.

Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation.

BACKGROUND AND OBJECTIVES: The Effect of a Reduction in GFR after Nephrectomy on Arterial Stiffness and Central Hemodynamics (EARNEST) study was a multicenter, prospective, controlled study designed to investigate the associations of an isolated reduction in kidney function on BP and arterial hemodynamics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective living kidney donors and healthy controls who fulfilled criteria for donation were recruited from centers with expertise in vascular research. Participants underwent office and ambulatory BP measurement, assessment of arterial stiffness, and biochemical tests at baseline and 12 months. RESULTS: A total of 469 participants were recruited, and 306 (168 donors and 138 controls) were followed up at 12 months. In the donor group, mean eGFR was 27 ml/min per 1.73 m2 lower than baseline at 12 months. Compared with baseline, at 12 months the mean within-group difference in ambulatory day systolic BP in donors was 0.1 mm Hg (95% confidence interval, -1.7 to 1.9) and 0.6 mm Hg (95% confidence interval, -0.7 to 2.0) in controls. The between-group difference was -0.5 mm Hg (95% confidence interval, -2.8 to 1.7; P=0.62). The mean within-group difference in pulse wave velocity in donors was 0.3 m/s (95% confidence interval, 0.1 to 0.4) and 0.2 m/s (95% confidence interval, -0.0 to 0.4) in controls. The between-group difference was 0.1 m/s (95% confidence interval, -0.2 to 0.3; P=0.49). CONCLUSIONS: Changes in ambulatory peripheral BP and pulse wave velocity in kidney donors at 12 months after nephrectomy were small and not different from controls. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: NCT01769924 (https://clinicaltrials.gov/ct2/show/NCT01769924).

What is new in the management of rapidly progressive glomerulonephritis?

Rapidly progressive glomerulonephritis (RPGN) results from severe crescentic damage to glomeruli and leads to irreversible kidney failure if not diagnosed and managed in a timely fashion. Traditional treatment has relied on glucocorticoids and cyclophosphamide, with additional plasmapheresis for certain conditions. Here we describe updates in the management of RPGN, according to the underlying renal pathology. However, there remains a paucity of trials that have enrolled patients with more advanced renal disease, dialysis dependence or with RPGN, and we are therefore still reliant on extrapolation of data from studies of patients with a less severe form of disease. In addition, reporting bias results in publication of cases or cohorts showing benefit for newer agents in advanced disease or RPGN, but it remains unclear how many unsuccessful outcomes in these circumstances take place. Since clinical trials specifically in RPGN are unlikely, use of biologic registries or combination of sufficient sized cohort series may provide indications of benefit outside of a clinical trial setting and should be encouraged, in order to provide some evidence for the efficacy of therapeutic regimens in RPGN and advanced renal disease.