In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). The guideline was derived from evidence available ...through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing AKI. In April of 2019, KDIGO held a controversies conference entitled Acute Kidney Injury with the following goals: determine best practices and areas of uncertainty in treating AKI; review key relevant literature published since the 2012 KDIGO AKI guideline; address ongoing controversial issues; identify new topics or issues to be revisited for the next iteration of the KDIGO AKI guideline; and outline research needed to improve AKI management. Here, we present the findings of this conference and describe key areas that future guidelines may address.
Vancomycin is the most frequently used antibiotic, accounting for up to 35% of hospitalized patients with infection, because of its optimal bactericidal effectiveness and relatively low price. ...Vancomycin-associated AKI (VA-AKI) is a clinically relevant but not yet clearly understood entity in critically ill patients. The current review comprehensively summarizes the pathophysiological mechanisms of, biomarkers for, preventive strategies for, and some crucial issues with VA-AKI. The pathological manifestations of VA-AKI include acute tubular necrosis, acute tubulointerstitial nephritis (ATIN), and intratubular crystal obstruction. The proposed pathological mechanisms of VA-AKI include oxidative stress and allergic reactions induced by vancomycin and vancomycin-associated tubular casts. Concomitant administration with other nephrotoxic antibiotics, such as piperacillin-tazobactam, high vancomycin doses, and intermittent infusion strategies compared to the continuous infusion are associated with a higher risk of VA-AKI. Several biomarkers could be applied to predict and diagnose VA-AKI. To date, no promising therapy is available. Oral steroids could be considered for patients with ATIN, whereas hemodialysis might be applied to remove vancomycin from the patient. In the future, disclosing more promising biomarkers that could precisely identify populations susceptible to VA-AKI and detect VA-AKI occurrence early on, and developing pharmacological agents that could prevent or treat VA-AKI, are the keys to improve the prognoses of patients with severe infection who probably need vancomycin therapy.
There exists a great knowledge gap in terms of long-term effects of various surgical and pharmacological treatments on outcomes among primary aldosteronism (PA) patients. Using a validated algorithm, ...we extracted longitudinal data for all PA patients diagnosed in 1997-2010 and treated in the Taiwan National Health Insurance. We identified 3362 PA patients for whom the mean length of follow-up was 5.75 years. PA has higher major cardiovascular events (MACE) than essential hypertension (23.3% vs 19.3%, p = 0.015). Results from the Cox model suggest a strong effect of adrenalectomy on lowering mortality (HR = 0.23 with residual hypertension and 0.21 with resolved hypertension). While the need for mineralocorticoid receptor antagonist (MRA) after diagnosis suggests that a defined daily dose (DDD) of MRA between 12.5 and 50 mg may alleviate risk of death in a U-shape pattern. A specificity test identified patients who has aldosterone producing adenoma (HR = 0.50, p = 0.005) also confirmed adrenalectomy attenuated all-cause mortality. Adrenalectomy decreases long-term all-cause mortality independently from PA cure from hypertension. Prescription corresponding to a DDD between 12.5 and 50 mg may decrease mortality for patients needing MRA. It calls for more attention on early diagnosis, early treatment and prescription of appropriate dosage of MRA for PA patients.
Context:
In patients who seek surgical cure of primary aldosteronism (PA), The Endocrine Society Guidelines recommend the use of adrenal vein sampling (AVS), which is invasive, technically ...challenging, difficult to interpret, and commonly held to be risky.
Objective:
The aim of this study was to determine the complication rate of AVS and the ways in which it is performed and interpreted at major referral centers.
Design and Settings:
The Adrenal Vein Sampling International Study is an observational, retrospective, multicenter study conducted at major referral centers for endocrine hypertension worldwide.
Participants:
Eligible centers were identified from those that had published on PA and/or AVS in the last decade.
Main Outcome Measure:
The protocols, interpretation, and costs of AVS were measured, as well as the rate of adrenal vein rupture and the rate of use of AVS.
Results:
Twenty of 24 eligible centers from Asia, Australia, North America, and Europe participated and provided information on 2604 AVS studies over a 6-yr period. The percentage of PA patients systematically submitted to AVS was 77% (median; 19–100%, range). Thirteen of the 20 centers used sequential catheterization, and seven used bilaterally simultaneous catheterization; cosyntropin stimulation was used in 11 centers. The overall rate of adrenal vein rupture was 0.61%. It correlated directly with the number of AVS performed at a particular center (P = 0.002) and inversely with the number of AVS performed by each radiologist (P = 0.007).
Conclusions:
Despite carrying a minimal risk of adrenal vein rupture and at variance with the guidelines, AVS is not used systematically at major referral centers worldwide. These findings represent an argument for defining guidelines for this clinically important but technically demanding procedure.
The clinical characteristics and outcomes in patients with clinical aldosterone-producing adenomas harboring
mutations with or without subclinical hypercortisolism remain unclear. This prospective ...study is aimed at determining factors associated with subclinical hypercortisolism in patients with clinical aldosterone-producing adenomas. Totally, 82 patients were recruited from November 2016 to March 2018 and underwent unilateral laparoscopic adrenalectomy with at least a 12-month follow-up postoperatively. Standard subclinical hypercortisolism (defined as cortisol >1.8 μg/dL after 1 mg dexamethasone suppression test DST) was detected in 22 (26.8%) of the 82 patients. Intriguingly, a generalized additive model identified the clinical aldosterone-producing adenoma patients with 1 mg DST>1.5 μg/dL had significantly larger tumors (
=0.02) than those with 1 mg DST<1.5 μg/dL. Multivariable logistic regression showed that the presence of
mutations (odds ratio, 0.22,
=0.010) and body mass index (odds ratio, 0.87,
=0.046) were negatively associated with 1 mg DST>1.5 μg/dL, whereas tumor size was positively associated with it (odds ratio, 2.85,
=0.014). Immunohistochemistry revealed a higher degree of immunoreactivity for CYP11B1 in adenomas with wild-type
(
=0.018), whereas CYP11B2 was more commonly detected in adenomas with
mutation (
=0.007). Patients with wild-type
and 1 mg DST>1.5 μg/dL exhibited the lowest complete clinical success rate (36.8%) after adrenalectomy. In conclusion, subclinical hypercortisolism is common in clinical aldosterone-producing adenoma patients without
mutation or with a relatively larger adrenal tumor. The presence of serum cortisol levels >1.5 μg/dL after 1 mg DST may be linked to a lower clinical complete success rate.
Microvascular pericytes and perivascular fibroblasts have recently been identified as the source of scar-producing myofibroblasts that appear after injury of the kidney. We show that cross talk ...between pericytes and endothelial cells concomitantly dictates development of fibrosis and loss of microvasculature after injury. When either platelet-derived growth factor receptor (R)-β signaling in pericytes or vascular endothelial growth factor (VEGF)R2 signaling in endothelial cells was blocked by circulating soluble receptor ectodomains, both fibrosis and capillary rarefaction were markedly attenuated during progressive kidney injury. Blockade of either receptor-mediated signaling pathway prevented pericyte differentiation and proliferation, but VEGFR2 blockade also attenuated recruitment of inflammatory macrophages throughout disease progression. Whereas injury down-regulated angiogenic VEGF164, the dys-angiogenic isomers VEGF120 and VEGF188 were up-regulated, suggesting that pericyte-myofibroblast differentiation triggers endothelial loss by a switch in secretion of VEGF isomers. These findings link fibrogenesis inextricably with microvascular rarefaction for the first time, add new significance to fibrogenesis, and identify novel therapeutic targets.
Objectives
Decreased glomerular filtration rate has been reported in patients with primary aldosteronism after unilateral adrenalectomy. Glomerular hyperfiltration has been assumed to mask the ...preoperative subtle renal impairment. In this study, we investigated predictors for decreased estimated glomerular filtration rate after adrenalectomy in patients with primary aldosteronism.
Methods
From January 2006 through September 2018, 328 patients with confirmatory diagnoses of primary aldosteronism received unilateral laparoscopic adrenalectomy and subsequent follow‐up for 12 months. We prospectively collected related parameters of the clinical outcomes and renal function to identify predictors of renal function impairment at 12 months after surgery.
Results
Patients were stratified into three groups by preoperative estimated glomerular filtration rate level: 144 (43.9%) with estimated glomerular filtration rate ≥90, 130 (39.6%) with estimated glomerular filtration rate within 60–89.9, and 54 (16.5%) with estimated glomerular filtration rate <60 mL/min/1.73 m2. The estimated glomerular filtration rate decreased significantly at the 6th month and remained stable at the 12th month, postoperatively. Patients with estimated glomerular filtration rate ≥90 had better clinical outcome with 59.6% success rate (P = 0.006) among three groups. Multivariate logistic regression analysis indicated that preoperative estimated glomerular filtration rate (odds ratio 1.012, P = 0.02) and hypokalemia (odds ratio 2.018, P = 0.024) were associated with renal impairment at 12th month after adrenalectomy. Multivariate linear regression analysis revealed high preoperative estimated glomerular filtration rate (β = 0.261, P < 0.001), high preoperative systolic blood pressure (β = 0.168, P = 0.003), high level of microalbuminuria (β = 0.024, P = 0.001), and low level of serum potassium (β = −4.883, P = 0.007) were associated with estimated glomerular filtration rate percentage decline at 12th month after adrenalectomy.
Conclusions
Estimated glomerular filtration rate declined significantly after adrenalectomy in patients with estimated glomerular filtration rate ≥90. The study provided important information to identify primary aldosteronism patients with higher risk of estimated glomerular filtration rate decline after adrenalectomy and might help to adopt early interventions to improve the outcomes.