Direct oral anticoagulants (DOACs) are increasingly used in renal transplant recipients (RTR), but relatively understudied in this population. We assess the safety of post-transplant anticoagulation ...with DOACs compared to warfarin.
We conducted a retrospective study of RTRs at the Mayo Clinic sites (2011-present) that were anticoagulated for greater than 3 months excluding the 1st month post-transplant. The main safety outcomes were bleeding and all-cause mortality. Concomitant antiplatelet and interacting drugs were noted. DOAC dose adjustment was assessed according to common US prescribing practices, guidelines, and/or FDA labeling.
The median follow-up was longer for RTRs on warfarin (1098 days IQR 521, 1517) than DOACs (449 days IQR 338, 942). Largely, there were no differences in baseline characteristics and comorbidities between RTRs on DOACs (n = 208; apixaban 91.3%, rivaroxaban 8.7%) versus warfarin (n = 320). There was no difference in post-transplant use of antiplatelets, immunosuppressants, most antifungals assessed, or amiodarone. There was no significant difference in incident major bleeding (8.4 vs. 5.3%, p = 0.89), GI bleeding (4.4% vs. 1.9%, p = 0.98), or intra-cranial hemorrhage (1.9% vs. 1.4%, p = 0.85) between warfarin and DOAC. There was no significant difference in mortality in the warfarin group compared to DOACs when adjusted for follow-up time (22.2% vs. 10.1%, p = 0.21). Rates of post-transplant venous thromboembolism, atrial fibrillation or stroke were similar between the two groups. 32% (n = 67) of patients on DOACs were dose reduced, where 51% of those reductions were warranted. 7% of patients that were not dose reduced should have been.
DOACs did not have inferior bleeding or mortality outcomes compared to warfarin in RTRs. There was greater use of warfarin compared to DOACs and a high rate of improper DOAC dose reduction.
The prevalence of nephrolithiasis has been on the rise over recent decades. There have also been extensive efforts to identify risk factors for chronic kidney disease (CKD). The purpose of this ...review is to highlight recent evidence on the association of nephrolithiasis with the development of CKD and end-stage renal disease (ESRD).
Several epidemiologic studies over the past decade assessed the relationship between history of nephrolithiasis and CKD. Across several studies, patients with nephrolithiasis had about a two-fold higher risk for decreased renal function or need for renal replacement therapy. This risk appears to be independent of risk factors for CKD that are common in stone formers such as hypertension and diabetes mellitus. Specific risk factors for CKD in stone formers include recurrent urinary tract infections, struvite and possibly uric acid stone composition, symptomatic stones, solitary kidney, ileal conduit, neurogenic bladder, and hydronephrosis.
Recent evidence has shown a consistent relationship between nephrolithiasis history and an increased risk of CKD and ESRD. Understanding the characteristics that predispose to CKD may better inform how to optimally manage patients with nephrolithiasis and prevent this complication.
The goal is to determine the delays and reduced rates of kidney transplant (KTx) for the Indigenous Americans and variables predictive of these outcomes at a large single transplant center.
300 ...Indigenous Americans and 300 non-Hispanic white American patients presenting for KTx evaluation from 2012-2016 were studied.
Compared to whites, the Indigenous Americans had the following: more diabetes, dialysis, physical limitation and worse socioeconomic characteristics(p<0.01); median difference of 20 day delay from referral to KTx evaluation, 17 day delay from approval to UNOS listing and 126.5 longer delay on the waitlist compared to whites(p<0.001). Of the Indigenous Americans listed, more died, were removed, or were still waiting than transplanted compared to whites (p<0.001). Variables predictive of delay from referral to transplant evaluation included: Indigenous race, distance from transplant center, coronary artery disease, and time on dialysis (p<0.05). Cumulative incidence of waitlisting and KTx was lower for Indigenous Americans (p<0.0001). Independent predictors of decreased likelihood of waitlisting included age, peripheral vascular disease, no caregiver, physical limitation, and illegal drug use history (p<0.05). Variables predictive of lower likelihood of KTx included Indigenous race, percentage of time inactive on the waitlist, no caregiver, and O blood type.
Among patients referred and evaluated for KTx, the Indigenous American race was independently associated with significant delays in the KTx process after accounting for co-morbid and socioeconomic factors. Cardiovascular morbidity and physical limitation were identified as important determinants of delay and decreased likelihood of waitlisting. Further quantitative and qualitative work is needed to identify and intervene on modifiable barriers to improve access to KTx for the Indigenous Americans.
The objective is to assess cardiovascular (CV), malignancy, infectious, graft outcomes and tacrolimus levels for the Indigenous patients compared to Whites after kidney transplant (KTx).
165 ...Indigenous and 165 White patients matched for the KTx year at Mayo Clinic Arizona from 2007-2015 were studied over a median follow-up of 3 years. Propensity score was calculated to account for baseline differences.
Compared to Whites, Indigenous patients had the following characteristics: younger age, more obesity, diabetes, hypertension, and required dialysis prior to KTx (p<0.01). Indigenous patients had longer hospital stay for KTx, shorter follow-up and lived further from the transplant center (p<0.05). 210 (63.6%) received deceased donor KTx and more Whites received a living donor KTx compared to Indigenous patients (55.2% vs 17.6%, p<0.0001). Post-KTx, there was no difference in the CV event rates. The cumulative incidence of infectious complications was higher among the Indigenous patients (HR 1.81, p = 0.0005, 48.5% vs 38.2%, p = 0.013), with urinary causes as the most common. Malignancy rates were increased among Whites (13.3% vs 3.0%, p = 0.001) with skin cancer being the most common. There was a significant increase in the dose normalized tacrolimus level for the Indigenous patients compared to Whites at 1 months, 3 months, and 1 year post-KTx. After adjustment for the propensity score, there was no statistical difference in infectious or graft outcomes between the two groups but the mean number of emergency room visits and hospitalizations after KTx was significantly higher for Whites compared to Indigenous patients.
Compared to Whites, Indigenous patients have similar CV events, graft outcomes and infectious complications after accounting for baseline differences.
Background The presence of a few renal cysts is considered of little relevance in healthy adults, although acquired renal cystic disease occurs in advanced kidney failure. The objective of this study ...was to detail renal cystic and solid lesions and identify any association with clinical characteristics. Study Design Clinical-pathologic correlation. Setting & Participants Potential kidney donors undergoing a standardized evaluation at the Mayo Clinic in 2000-2008. Predictors Age, kidney function, and chronic kidney disease risk factors. Measurements Renal cystic and solid lesions by contrast-enhanced computed tomographic images. Outcomes Cyst number, diameter, and location. Results After excluding 8 with cystic disease, 7 of whom had autosomal dominant polycystic kidney disease, there were 1,948 potential kidney donors (42% men; mean age, 43 years). A cortical, medullary, or parapelvic cyst ≥5 mm was present in 12%, 14%, or 2.8%. For ages 19-49 years, 39%, 22%, 7.9%, and 1.6% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. For ages 50-75 years, 63%, 43%, 22%, and 7.8% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. The 97.5th percentile for number of cortical and medullary cysts ≥5 mm increased with age (10 for men and 4 for women in the 60- to 69-year group). After age and sex adjustment, cortical and medullary cysts ≥5 mm were associated with higher 24-hour urine albumin excretion, as well as increased body surface area, hypertension, and higher glomerular filtration rate in some analyses. Angiomyolipomas, hyperdense cysts, and enhancing masses or cysts with concerning features for malignancy occurred in 2.2%, 1.2%, and 0.6% and were associated with older age ( P ≤ 0.05 for each). Limitations Persons with known chronic kidney disease were excluded. Conclusions Renal cysts are common, particularly in older men, and may be a marker of early kidney injury because they associate with albuminuria, hypertension, and hyperfiltration.
Current knowledge of risk factors and renal histologic patterns of oxalate nephropathy (ON) not due to primary hyperoxaluria (PH) has been limited to small case series and case reports. Thus, we ...analyzed and compared clinical risk factors, histologic characteristics, and renal outcomes of patients with biopsy-confirmed ON among a cohort of patients with enteric and nonenteric risk factors.
A clinical data repository of native kidney pathology reports from 2009 to 2020 at all Mayo Clinic sites was used to identify 421 ON cases.
After excluding cases in transplanted kidneys or due to PH, 64 cases remained. Enteric risk factors were present in 30 and nonenteric in 34. Roux-en-Y gastric bypass (17) and pancreatic insufficiency (6) were most common in the enteric hyperoxaluria group. In the nonenteric group, vitamin C (7) and dietary oxalate (7) were common, while no apparent risk was noted in 16. Acute kidney injury (AKI) stage III at the time of diagnosis was present in 60%, and 40.6% required dialysis. Patients in the nonenteric group had more interstitial inflammation (p = 0.01), and a greater number of tubules contained intratubular calcium oxalate (CaOx) crystals (p = 0.001) than the nonenteric group. Patients in the enteric group were more likely to have baseline chronic kidney disease (CKD) (p = 0.02) and moderate-to-severe tubulointerstitial fibrosis and atrophy (IFTA) (OR 3.49, p = 0.02). After a median follow-up of 10 months, 39% were dialysis dependent, 11% received a kidney transplant, and 32% died. On univariate analysis, >10 tubules with CaOx crystals, baseline CKD, and AKI requiring dialysis correlated with the risk of dialysis, transplant, or death. On multivariate analysis, only AKI requiring dialysis correlated with adverse renal outcomes.
This is the largest cohort study of ON not due to PH. Histologic features differ in patients with enteric versus nonenteric risks. Patients in the enteric group are more likely to have baseline CKD and significant IFTA, while patients in the nonenteric group were more likely to have a greater number of tubules with CaOx crystals and corresponding interstitial inflammation. AKI requiring dialysis at the time of diagnosis was the single most significant predictor of adverse renal outcome.
ABSTRACT
Background
Serum cystatin C–based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine–based eGFR (eGFRcr) despite similar ...precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients.
Methods
Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors.
Results
There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P < .001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P < .001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P < .001) and CV events or mortality (HR 1.49, P < .001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated.
Conclusion
eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.
Graphical Abstract
Graphical Abstract
Solubility of Tumorigenicity 2 (sST2) is a novel biomarker that better stratifies risk of cardiovascular events (CVE) compared to cardiac troponin T(cTnT) in heart failure. We assessed the ...association of sST2 with the composite outcome of CVE and/or mortality compared to cTnT in kidney transplant candidates.
200 kidney transplant candidates between 2010 and 2013 were included. Elevated sST2 was defined as ≥30ng/ml, cTnT≥0.01 ng/ml.
Median age 53 (interquartile range (IQR) 42-61) years, 59.7% male and 82.0% white. 33.5% had history of CVE, 42.5% left ventricular hypertrophy (LVH) and 15.6% positive cardiac stress test. Elevated sST2 correlated with male gender, history of prior-transplants, CVE, positive stress test, LVH, elevated cTnT, anemia, hyperphosphatemia, increased CRP and non-transplanted status. Male gender, history of CVE and LVH were independent determinants of sST2. During 28 months (IQR 25.3-30), 7.5% died, 13.0% developed CVE and 19.0% developed the composite outcome. Elevated sST2 was associated with the composite outcome (hazard ratio = 1.76, CI 1.06-2.73, p = 0.029) on univariate analysis but not after adjusting for age, diabetes and cTnT (p = 0.068). sST2 did not change the risk prediction model for composite outcome after including age, diabetes, prior history of CVE and elevated cTnT.
Increased sST2 level is significantly associated with variables associated with CVE in kidney transplant candidates. sST2 was associated with increased risk of the composite outcome of CVE and/or death but not independent of cTnT. Larger studies are needed to confirm these findings and determine whether sST2 has added value in CV risk stratification in this cohort of patients.
Pericardial disease is a recognized manifestation of cardiovascular disease in the end-stage renal disease (ESRD) population, and can manifest as pericardial effusion, though the prognosis of ...pericardial disease in ESRD patients is unclear. In the modern era of renal replacement therapy, little is known about the prevalence and the implications of pericardial effusion in ESRD patients, its echocardiographic characteristics, and risk factors. We conducted a retrospective chart review on subjects > than 18 years of age with known ESRD who were undergoing outpatient evaluation for renal transplantation at Mayo Clinic Arizona between January 2001 and December 2015 and had baseline echocardiogram completed within 3 months of their initial evaluation. Patients with moderate sized pericardial effusions or larger were identified. The pericardial effusion cohort was age and gender matched with a cohort of patients with ESRD without pericardial effusion in a 1:2 fashion. 54 patients with moderate or greater sized pericardial effusion out of 2,820 patients that fit our inclusion criteria, corresponding to a prevalence of 1.9%. A total of 41 patients or 75.9%, had a moderate sized effusion. A total of 13 patients, or 24.1% had a large sized effusion, 7 of whom had tamponade physiology on echocardiography. The presence and size of the effusion was not predictive for worse outcomes. Hemodialysis duration was protective, but no other factors were predictive or protective in the development of moderate sized or larger pericardial effusions, including echocardiographic parameters.
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