Acute Kidney Injury After Total Hip and Knee Arthroplasty. What Is the Culprit?

Background: Acute kidney injury (AKI) is associated with increased complications after total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to determine the risk factors for AKI after THA and TKA and evaluate if preoperative use of antihypertensive drugs is a risk factor for AKI. Methods: A retrospective review of 7406 primary TKAs and THAs (4532 hips and 2874 knees) from 2013 to 2019 was performed. The following preoperative variables were obtained from medical records: medications, chemistry 7 panel, Elixhauser comorbidities, and demographic factors. AKI was defined as an increase in serum creatinine by 26.4 µmol·L-1. Multivariate analysis was performed to identify the risk factors. Results: The overall incidence of postoperative AKI was 6.2% (n = 459). Risk factors for postoperative AKI were found to be: chronic kidney disease (odds ratio [OR] = 7.09; 95% confidence interval [CI]: 4.8-9.4), diabetes (OR: 5.03; 95% CI: 2.8-6.06), ≥3 antihypertensive drugs (OR: 4.2; 95% CI: 2.1-6.2), preoperative use of an angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (OR: 3.8; 95% CI: 2.2-5.9), perioperative vancomycin (OR: 2.7; 95% CI: 1.8-4.6), and body mass index >40 kg/m2 (OR: 1.9; 95% CI: 1.3-3.06). Conclusions: We have identified several modifiable risk factors for AKI that can be optimized prior to an elective THA or TKA. The use of certain antihypertensive agents namely angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and multidrug antihypertensive regimens were found to significantly increase the risk of AKI. Therefore, perioperative management of patients undergoing joint replacement should include medical comanagement with a focus on careful management of antihypertensives.

Update in Hypertension.

The treatment of elevated blood pressure (BP) can improve cardiovascular (CV) event rates. Current BP targets depend on expected CV event rates in individuals as assessed by concurrent medical conditions and other risk factors. Importantly, the means by which BP is measured has evolved. This evolution is driven by recognition that techniques different than routine office BP measurements can provide a better assessment of future CV risk.

Determination of Optical Properties and Photodynamic Threshold of Lung Tissue for Treatment Planning of In Vivo Lung Perfusion Assisted Photodynamic Therapy.

BACKGROUND: Isolated lung metastases in sarcoma and colorectal cancer patients are inadequately treated with current standard therapies. In Vivo Lung Perfusion, a novel platform, could overcome limitations to photodynamic therapy treatment volumes by using low cellular perfusate, removing blood, theoretically allowing greater light penetration. To develop personalized photodynamic therapy protocols requires in silico light propagation simulations based on optical properties and maximal permissible photodynamic threshold dose of lung tissue. This study presents quantification of optical properties for two perfusates and the photodynamic threshold for 5-ALA and Chlorin e6. METHODS: Porcine and human lungs were placed on Ex Vivo Lung Perfusion, and perfused with acellular solution or blood. Isotropic diffusers were placed within bronchi and on lung surface for light transmission measurements, from which absorption and light scattering properties were calculated at multiple wavelengths. Separately, pigs were injected with 5-ALA or Chlorin e6, and lung tissue was irradiated at increasing doses. Resultant lesion sizes were measured by CT and histology to quantify the photodynamic threshold. RESULTS: Low cellular perfusate reduced the tissue absorption coefficient significantly, increasing penetration depth of light by 3.3 mm and treatment volumes 3-fold. The photodynamic threshold for lung exposed to 5-ALA was consistent with other malignancies. Chlorin e6 levels were undetectable in lung tissue and did not demonstrate photodynamic-induced necrosis. CONCLUSIONS: Light penetration with low cellular perfusate is significantly greater and could enable treatments for diffuse disease. This data aids photodynamic treatment planning and will guide clinical translation of photodynamic therapy protocols in the lung, especially during lung perfusion.

Prevalence of true therapeutic inertia in blood pressure control in an academic chronic kidney disease clinic.

Therapeutic inertia (TI) in blood pressure (BP) control has been traditionally defined as failure to initiate or intensify therapy when treatment goals are not met. The fallacy with this definition is that TI may be overestimated because it includes hypertensive patients deliberately uncontrolled. This is a retrospective chart review study that evaluated physicians' response to an uncontrolled clinic BP reading in a population of patients with stage 3 to 5 chronic kidney disease (CKD) and hypertension. Of 429 patients screened, 166 had controlled BP and 263 did not. Of these 263 patients, 115 patients had no clear reason documented for the absence of changes in medication regimen. This population was defined as cases with true TI. In the remaining 148 patients, the medication regimen was changed in 81 patients. In the rest of the patients, there was a reason documented for not changing the medication regimen. The prevalence of true TI rate (defined as percentage of uncontrolled hypertension as a result of physician inaccountability) in our study was 44% as compared with 69% if the traditional TI definition is applied. Thus, we conclude that the prevalence of TI in the literature overestimates the rate of true TI as it does not account for physician decision making. The current definition of TI in BP control needs to be revised, as it underestimates a provider's care to improve BP control and is misleading. The TI definition should include some mechanism to account for interventions beyond medication titration.

Treatment of lactic acidosis: appropriate confusion.

BACKGROUND: Lactic acidosis (LA) is common in hospitalized patients and is associated with poor clinical outcomes. There have been major recent advances in our understanding of lactate generation and physiology. However, treatment of LA is an area of controversy and uncertainty, and the use of agents to raise pH is not clearly beneficial. AIM AND METHODS: We reviewed animal and human studies on the pathogenesis, impact, and treatment of LA, published in the English language and available through the PubMed/MEDLINE database. Our aim was to clarify the physiology of the generation of LA, its impact on outcomes, and the different treatment modalities available. We also examined relevant data regarding LA induced by medications commonly prescribed by hospitalists: biguanides, nucleoside analog reverse-transcriptase inhibitors (NRTIs), linezolid, and lorazepam. RESULTS/CONCLUSIONS: Lactic acid is a marker of tissue ischemia but it also may accumulate without tissue hypoperfusion. In the latter circumstance, lactic acid accumulation may be an adaptive mechanism-a novel possibility quite in contrast to the traditional view of lactic acid as only a marker of tissue ischemia. Studies on the treatment of LA with sodium bicarbonate or other buffers fail to show consistent clinical benefit. Severe acidemia in the setting of LA is a particularly poorly studied area. In the settings of medication-induced LA, optimal treatment, apart from prompt cessation of the offending agent, is still unclear.

Salt intake and insulin sensitivity in healthy human volunteers.

The literature on salt intake and insulin sensitivity presents a mixed picture, as some studies have shown an increase, whereas others have shown a decrease, in insulin action as sodium intake is enhanced. In some cases, this may relate to the study of salt intake in patients with co-morbidities such as hypertension or diabetes. In the present study, we selected healthy normotensive lean volunteers who underwent a euglycaemic clamp following 6 days of a low-salt diet (20 mmol sodium daily) and, subsequently, 6 days of a high-salt diet (200 mmol sodium daily). Our results show an increase in insulin-mediated glucose disposal during euglycaemic clamp conditions that was significantly higher following the high-salt diet compared with the low-salt diet (7.41+/-0.41 compared with 6.11+/-0.40 mg x kg(-1) of body weight x min(-1) respectively; P=0.03). We measured calf blood flow before and during insulin infusion (no significant change after the two dietary salt interventions was detected) and plasma non-esterified fatty acids (also no significant differences were detected). We observed the expected increases in renin concentration and aldosterone activity in subjects on the low-salt diet, and also observed a significantly less increase in plasma noradrenaline concentration during euglycaemic insulin infusion following the high-salt compared with the low-salt diet. We propose that the 4-5-fold increase in serum aldosterone and the greater increase in plasma noradrenaline concentration following the low-salt intervention compared with the high-salt period may have contributed to the differences in insulin sensitivity following the adjustment in dietary sodium intake.

Systematic review of the effect of daily alcohol intake on blood pressure.

Numerous epidemiologic investigations have found an association between moderate intake of alcohol and increased blood pressure (BP). However, in controlled clinical studies that directly tested the effects of alcohol intake on BP, findings are inconsistent, perhaps because of differences in duration of alcohol use and the timing of BP measurements. In this setting, we performed a systematic review of trials that measured BP after a period of sustained alcohol intake (defined as daily intake of at least one alcoholic drink daily) in one group and that also had a control group of individuals who consumed no alcohol. Nine studies met the entrance criteria. The review demonstrated a significant rise in systolic blood pressure (SBP) and diastolic BP (DBP) of 2.7 mm and 1.4 mm Hg, respectively, after alcohol intake. An early effect of alcohol leading to a reduction BP (in the hours after exposure) and a later effect (next day) of raising BP led to smaller differences in the net effect of alcohol on BP when ambulatory BP monitoring measurements were compared with casual office- or clinic-based measurements. Our findings may have important implications for interpreting studies measuring the effect of alcohol on BP as well as for regular clinical care. These findings indicate that the timing of BP measurements after alcohol intake has a substantial effect on the magnitude and perhaps even the direction of BP change.

A randomized, double-blind, placebo-controlled trial of casein protein hydrolysate (C12 peptide) in human essential hypertension.

BACKGROUND: Many patients seek complementary medicine treatments like neutraceuticals for common conditions such as hypertension. METHODS: We conducted a placebo-controlled prospective randomized crossover study in 10 hypertensive subjects to determine whether a single dose of a hydrolysate of bovine milk protein (designated C12 peptide; low and high dose), either alone or combined with alginic acid (low and high dose), reduced daytime blood pressure (BP), as determined by ambulatory BP monitoring. RESULTS: Within the five treatment regimens a significant reduction of 9.2 +/- 3.2 mm Hg in systolic BP at h 6 compared with h 2 occurred on the higher dose of alginic acid (1754 mg) combined with C12 (P = .02). The C12 peptide with the higher dose of alginic acid also showed a significant reduction of 6.0 +/- 2.0 mm Hg in diastolic BP at h 6 compared with h 2 (P = .015). CONCLUSIONS: These preliminary data are encouraging and deserve testing in a larger and longer treatment trial.

Willingness of dialysis patients to participate in a randomized controlled trial of daily dialysis.

BACKGROUND: The National Institutes of Health (NIH) has proposed conducting randomized controlled trials comparing short, daily, in-center hemodialysis with conventional hemodialysis. However, there is concern that difficulties recruiting patients may prevent the successful completion of such trials if patients believe the inconveniences of daily dialysis outweigh any potential health benefits. METHODS: To gauge willingness to participate in a daily dialysis trial, we described a hypothetical, randomized controlled trial comparing conventional to daily hemodialysis to 209 chronic hemodialysis patients, and assessed their motivations for and concerns about participating. RESULTS: We found that 85 patients (41%) of 209 patients who agreed to be interviewed expressed some willingness to participate in the hypothetical trial. Patients who expressed greater willingness to participate were younger (OR for participating = 0.96 per year, 95% CI = 0.94 to 0.98, P= 0.001), less likely to smoke (OR = 0.38, 95% CI = 0.17 to 0.84, P= 0.017), more likely to have been hospitalized during the last 12 months (OR = 2.8, 95% CI = 1.5 to 5.5, P= 0.002), less likely to have reactive airway disease (OR = 0.21, 95% CI = 0.06 to 0.69, P= 0.01) or coronary artery disease (OR = 0.20, 95% CI = 0.08 to 0.53, P= 0.001), and less likely to be on the waiting list for a kidney transplant (OR = 0.23, 95% CI = 0.10 to 0.50, P < 0.0001). CONCLUSION: The study suggests that less than half of eligible patients would be willing to participate in the randomized controlled trial. Differing willingness to participate across patient subgroups suggests that certain subgroups (i.e., older patients and those with coronary artery disease) will need to be targeted to ensure that results are generalizable to most hemodialysis patients.