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.

Symmetric dimethylarginine is a stronger predictor of mortality risk than asymmetric dimethylarginine among older people with kidney disease.

BACKGROUND: Circulating asymmetric dimethylarginine and symmetric dimethylarginine are increased in patients with kidney disease. Symmetric dimethylarginine is considered a good marker of glomerular filtration rate, while asymmetric dimethylarginine is a marker of cardiovascular risk. However, a link between symmetric dimethylarginine and all-cause mortality has been reported. In the present study, we evaluated both dimethylarginines as risk and glomerular filtration rate markers in a cohort of elderly white individuals, both with and without chronic kidney disease. METHODS: Glomerular filtration rate was measured in 394 individuals aged >74 years using an iohexol clearance method. Plasma asymmetric dimethylarginine, symmetric dimethylarginine and iohexol were measured simultaneously using isotope dilution tandem mass spectrometry. RESULTS: Plasma asymmetric dimethylarginine concentrations were increased ( P < 0.01) in people with glomerular filtration rate <60 mL/min/1.73 m2 compared with those with glomerular filtration rate ≥60 mL/min/1.73 m2, but did not differ ( P > 0.05) between those with glomerular filtration rate 30-59 mL/min/1.73 m2 and <30 mL/min/1.73 m2. Plasma symmetric dimethylarginine increased consistently across declining glomerular filtration rate categories ( P < 0.0001). Glomerular filtration rate had an independent effect on plasma asymmetric dimethylarginine concentration, while glomerular filtration rate, gender, body mass index and haemoglobin had independent effects on plasma symmetric dimethylarginine concentration. Participants were followed up for a median of 33 months. There were 65 deaths. High plasma asymmetric dimethylarginine ( P = 0.0412) and symmetric dimethylarginine ( P < 0.0001) concentrations were independently associated with reduced survival. CONCLUSIONS: Among elderly white individuals with a range of kidney function, symmetric dimethylarginine was a better marker of glomerular filtration rate and a stronger predictor of outcome than asymmetric dimethylarginine. Future studies should further evaluate the role of symmetric dimethylarginine as a marker of outcome and assess its potential value as a marker of glomerular filtration rate.

The impact of pay for performance on the control of blood pressure in people with chronic kidney disease stage 3-5.

BACKGROUND: The implementation of national estimated glomerular filatration rate reporting and the inclusion of renal-specific indicators in a primary care pay for performance (P4P) system since April 2006 has promoted identification and better management of risk factors related to chronic kidney disease (CKD). In the UK, the P4P framework is known as the Quality and Outcomes Framework (QOF). One of the key targets for intervention in primary care was hypertension. It is clear that hypertension is a major predictor of development and progression of CKD; thus, targeting better blood pressure control is likely to have a positive impact on outcomes in CKD. The aim of this study was to evaluate the effectiveness of renal indicators outlined in P4P on the management of hypertension in primary care. To estimate the cost implications of the resulting changes in prescribing patterns of antihypertensive medication following introduction of such indicators. METHODS: We performed a prospective cohort study using a large primary care database. This cohort was taken from a database collated as part of a clinical decision support system used to assist the management of CKD in primary care. We investigated a total population of 90 250 individuals on general practitioner (GP) registers with a valid serum creatinine estimation in the 6-year study period. A total of 10 040 patients had confirmed stage 3-5 CKD in the 2 years pre-QOF and formed the study cohort. Patients were studied over three time periods, pre-QOF (1 April 2004 to 31 March 2006), 2 years post-QOF (1 April 2006 to 31 March 2008) and finally the two subsequent years (1 April 2008 to 31 March 2010). The mean systolic and diastolic blood pressures (BP) together with antihypertensive medication were analysed over the three time periods. Cost calculation was based on 2009 British National Formulary list prices for antihypertensives. RESULTS: The mean age of the cohort at the start of the study period was 64.8 years, 55% were female. In those patients with stage 3-5 CKD 83.9% were hypertensive, defined by a pre-P4P BP of >140/85 or currently taking antihypertensive medication. The proportion of patients with CKD 3-5 attaining the BP target of 145/80 increased from 41.5% in the pre-QOF period to 50.0% in the post-QOF period. This increase was even more marked for those with hypertension in the pre-QOF period (28.8-45.1%). In the hypertensive patients, mean BP fell from 146/79 mmHg to 140/76 in the first 2 years post-P4P [P < 0.01, analysis of variance (ANOVA)]. This BP reduction was sustained in the last 2 years of the study, 139/75 (P < 0.01, ANOVA). The proportion of hypertensive patients taking angiotensin-converting enzyme inhibitors or angiotensin blockers increased, this was also sustained in the third time period. An increase in the prescribing of diuretics, calcium channel blockers and ß-blockers was also observed. The additional cost of increased prescribing was calculated to be €25.00 per hypertensive patient based on GP prescription data. CONCLUSIONS: Population BP control has improved since the introduction of P4P renal indicators, and this improvement has been sustained. This was associated with a significant increase in the use of antihypertensive medication, resulting in increased prescription cost. Longer-term follow-up will establish whether or not this translates to improved outcomes in terms of progression of CKD, cardiovascular disease and patient mortality.

Accuracy of the MDRD (Modification of Diet in Renal Disease) study and CKD-EPI (CKD Epidemiology Collaboration) equations for estimation of GFR in the elderly.

BACKGROUND: Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated using equations that adjust serum creatinine concentration for age, race, and sex. The Modification of Diet in Renal Disease (MDRD) Study equation is widely used, but underestimates GFR at higher levels. The serum creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI(cr)) equation generally provides more accurate estimation at GFR >60 mL/min/1.73 m(2). Newer equations have been reported using cystatin C concentration either alone (CKD-EPI(cys)) or in combination with creatinine concentration (CKD-EPI(cr-cys)). None of these equations has been well validated in older people. We tested the accuracy of these equations in people 74 years or older compared with GFR measured by a reference method. STUDY DESIGN: Diagnostic test evaluation in a prospective cohort. SETTING & PARTICIPANTS: Participants (n = 394; median age, 80 [range, 74-97] years) recruited from nephrology clinics and the community. INDEX TEST: GFR estimated using the MDRD Study, CKD-EPI(cr), CKD-EPI(cys) and CKD-EPI(cr-cys) equations. REFERENCE TEST: GFR measured using an iohexol clearance method. RESULTS: Median measured GFR was 53.4 (range, 7.2-100.9) mL/min/1.73 m(2). MDRD Study-, CKD-EPI(cr)-, and CKD-EPI(cr-cys)-estimated GFRs overestimated GFR (median differences of 3.5 [P< 0.001], 1.7 [P < 0.001], and 0.8 [P = 0.02] mL/min/1.73 m(2), respectively); the CKD-EPI(cys) equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR [P(30)]) was 81%, 83%, 86%, and 86% for the MDRD Study, CKD-EPI(cr), CKD-EPI(cys), and CKD-EPI(cr-cys) equations, respectively. Accuracy of the MDRD Study equation was inferior (P = 0.004) to the CKD-EPI(cr) equation at GFR >60 mL/min/1.73 m(2). LIMITATIONS: Those of non-European ancestry were not included. For practical reasons, only a 4-hour sampling protocol was used for iohexol clearance. CONCLUSIONS: The CKD-EPI(cr) equation appeared less biased and was more accurate than the MDRD Study equation. No equation achieved an ideal P(30) in the overall population. Our data suggest that GFR estimation is as satisfactory in older people of European ancestry as it has been reported to be in younger individuals.