Signals From Inflamed Perivascular Adipose Tissue Contribute to Small Vessel Dysfunction in Women Living With the Human Immunodeficiency Virus.

INTRODUCTION: People living with the human immunodeficiency virus (PWH) have microvascular disease. Since perivascular adipose tissue (PVAT) regulates microvascular function and adipose tissue is inflamed in PWH, we tested the hypothesis that PWH have inflamed PVAT that impairs the function of their small vessels. METHODS: Subcutaneous small arteries were dissected with or without (+ or -) PVAT from a gluteal skin biopsy from 11 women with treated HIV (WWH) aged < 50 years and 10 matched women without HIV and studied on isometric myographs. Nitric oxide (NO) and reactive oxygen species (ROS) were measured by fluorescence microscopy. Adipokines and markers of inflammation and ROS were assayed in PVAT. RESULTS: PVAT surrounding the small arteries in control women significantly (P < 0.05) enhanced acetylcholine (Ach)-induced endothelium dependent relaxation and NO and reduced contractions to thromboxane and endothelin-1. However, these effects of PVAT were reduced significantly (P < 0.05) in WWH whose PVAT released less adiponectin but more markers of ROS and inflammation. Moderation of contractions by PVAT were correlated positively with adipose adiponectin. CONCLUSION: PVAT from WWH has oxidative stress, inflammation and reduced release of adiponectin that may contribute to enhanced contractions and therefore could promote small artery dysfunction.

Pathways to improve nephrologist comfort in managing patients on in-center or home self-care dialysis.

In end-stage kidney disease (ESKD), patient engagement and empowerment are associated with improved survival and complications. However, patients lack education and confidence to participate in self-care. The development of in center self-care hemodialysis can enable motivated patients to allocate autonomy, increase satisfaction and engagement, reduce human resource intensiveness, and cultivate a curiosity about home dialysis. In this review, we emphasize the role of education to overcome barriers to home dialysis, strategies of improving home dialysis utilization in the COVID 19 era, the significance of in-center self-care dialysis (e.g., cost containment and empowering patients), and implementation of an in-center self-care dialysis as a bridge to home hemodialysis (HHD).

Etiology and Management of Edema: A Review.

The development of peripheral edema can often pose a significant diagnostic and therapeutic challenge for practitioners due to its association with a wide variety of underlying disorders ranging in severity. Updates to the original Starling's principle have provided new mechanistic insights into edema formation. Additionally, contemporary data highlighting the role of hypochloremia in the development of diuretic resistance provide a possible new therapeutic target. This article reviews the pathophysiology of edema formation and discusses implications for treatment.

Current Trends and Challenges in Nephrology Fellowship Training: Expansion of Education in Home Dialysis, Palliative Care, and Point-of-Care Ultrasound.

Nephrology education has changed significantly since the first nephrology fellowship programs were established in the United States in the 1950s and 1960s. The past several years have seen increased opportunities for subspecialization in areas such as interventional nephrology, onconephrology, and glomerular disease. Notable trends in fellowship curricula include the expansion of education in home dialysis and palliative care, driven by policy changes and focus on patient-centered care. In addition, point-of-care ultrasound has garnered significant interest due to its potential to provide diagnostic information that improves patient care. An important area that remains largely unaddressed appears to be education about the business and administrative aspects of nephrology. Meanwhile, the importance of training in hemodialysis catheter placement and kidney biopsy has come into question due to the small proportion of nephrologists performing these procedures today. Nephrology fellowship programs should strive to tailor their curriculum to meet the interests and needs of individual fellows.

Pseudohyperkalemia: Three Cases and a Review of Literature.

Hyperkalemia is a potentially fatal complication requiring prompt diagnosis and management. However, pseudohyperkalemia, defined as an artificial rise in serum potassium (Sk), is also an important diagnosis because management differs. Pseudohyperkalemia can result from multiple factors, including excessive potassium leakage from cells of the forearm during blood collection due to release from exercising the muscle during fist clenching, while washout is prevented by tourniquet application, hemolysis, problems with sample transport, preanalysis or contamination, cell damage and metabolic changes, familial conditions that permit excessive potassium ion (K+) leak from erythrocytes after blood sampling, and leukocytosis or thrombocytosis. In this review, we will discuss the major causes of pseudohyperkalemia, how to avoid certain diagnostic pitfalls, and comment on the clinical importance of recognizing these false readings. We will review three clinical cases seen in our nephrology and hypertension clinic that illustrate some of these problems.

The utility of trough mycophenolic acid levels for the management of lupus nephritis.

Background: Monitoring of mycophenolic acid (MPA) levels may be useful for effective mycophenolate mofetil (MMF) dosing. However, whether commonly obtained trough levels are an acceptable method of surveillance remains debatable. We hypothesized that trough levels of MPA would be a poor predictor of area under the curve (AUC) for MPA. Methods: A total of 51 patients with lupus nephritis who were on MMF 1500 mg twice a day and had a 4-h AUC done were included in this study. MPA levels were measured prior to (C0) and at 1 (C1), 2 (C2) and 4 (C4) h, followed by 1500 mg of MMF. The MPA AUC values were calculated using the linear trapezoidal rule. Regression analysis was used to examine the relationship between the MPA trough and AUC. Differences in the MPA trough and AUC between different clinical and demographic categories were compared using t-tests. Results: When grouped by tertiles there was significant overlap in MPA, AUC 0-4 and MPA trough in all tertiles. Although there was a statistically significant correlation between MPA trough levels and AUC, this association was weak and accounted for only 30% of the variability in MPA trough levels. This relationship might be even more unreliable in men than women. The use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with increased MPA trough levels and AUC at 0-4 h (AUC0-4). Conclusion: Trough levels of MPA do not show a strong correlation with AUC. In clinical situations where MPA levels are essential to guide therapy, an AUC0-4 would be a better indicator of the adequacy of treatment.

Thiazide Therapy in Chronic Kidney Disease: Renal and Extra Renal Targets.

BACKGROUND: Thiazides are the most commonly used medications for the treatment of mild and moderate hypertension. Despite their recognized effect, the mechanism by which thiazides reduce systemic blood pressure remains uncertain. The prevailing belief is that thiazides reduce blood pressure primarily via enhancement of salt excretion consequent to the inhibition of the Na-Cl Cotransporter (NCC) in the Distal Convoluted Tubules (DCT). However, recent reports point to a reduction in peripheral vascular resistance as a major mechanism of antihypertensive effect of thiazides. It is plausible that both mechanisms, renal and extra-renal, may be operating simultaneously. Recent studies point to compensatory mechanisms in the kidney distal nephron that may play a role in blunting the diuretic effect of thiazides. Not much information is available about the efficacy of thiazides in controlling blood pressure in individuals with Chronic Kidney Disease (CKD). OBJECTIVE: This review will discuss the latest updates on the use and efficacy of thiazides derivatives as diuretics and antihypertensive medications in CKD patients. CONCLUSION: Thiazides remain effective as diuretics and antihypertensive agents in individuals with low GFR.

Pulmonary and tricuspid valvuloplasty in carcinoid heart disease.

A 26-year-old female with carcinoid heart disease consisting of severe pulmonary and tricuspid valve stenosis was admitted with line associated sepsis. She recovered from sepsis with antibiotics and aggressive fluid resuscitation but became grossly volume overloaded with evidence of tense ascites and lower extremity edema. She developed worsening renal and hepatic function due to congestive nephropathy and hepatopathy, which did not respond to intravenous diuretics, and she was deemed too sick for surgical pulmonary and tricuspid valve replacement. Pulmonary and tricuspid valvuloplasty was performed as a rescue measure to alleviate her congestive symptoms and improve her candidacy for valve replacement. © 2016 Wiley Periodicals, Inc.

Urine Ammonium, Metabolic Acidosis and Progression of Chronic Kidney Disease.

The metabolism of a typical Western diet generates 50-100 mEq of acid (H+) per day, which must be excreted in the urine for the systemic acid-base to remain in balance. The 2 major mechanisms that are responsible for the renal elimination of daily acid under normal conditions are ammonium (NH4+) excretion and titratable acidity. In the presence of systemic acidosis, ammonium excretion is intensified and becomes the crucial mechanism for the elimination of acid. The impairment in NH4+ excretion is therefore associated with reduced acid excretion, which causes excess accumulation of acid in the body and consequently results in metabolic acidosis. Chronic kidney disease (CKD) is associated with the impairment in acid excretion and precipitation of metabolic acidosis, which has an adverse effect on the progression of CKD. Recent studies suggest that the progressive decline in renal ammonium excretion in CKD is an important determinant of the ensuing systemic metabolic acidosis and is an independent factor for predicting the worsening of kidney function. While these studies have been primarily performed in hypertensive individuals with CKD, a closer look at renal NH4+ excretion in non-hypertensive individuals with CKD is warranted to ascertain its role in the progression of kidney disease.

Babesiosis: An unusual cause of sepsis after kidney transplantation and review of the literature.

We report a unique case of babesiosis presenting as sepsis after kidney transplantation. A 70-year-old female kidney transplant recipient presented with fever, hemolytic anemia, and acute kidney injury, and met three of four systemic inflammatory response syndrome criteria. Serology was positive for Babesia microti, confirmed by polymerase chain reaction. The patient was treated with atovaquone and azithromycin and made a full recovery. Reports of babesiosis after solid organ transplantation are rare, with only four prior cases reported in the literature. We report the first case of babesiosis, to our knowledge, presenting as sepsis that was successfully treated after solid organ transplantation.

High-risk Trans-Catheter Aortic Valve Replacement in a Failed Freestyle Valve with Low Coronary Height: A Case Report.

A 55-year-old male with a history of two prior cardiac surgeries presented with decompensated heart failure due to severe bioprosthetic aortic valve insufficiency. A third operation was viewed prohibitively high risk and valve-in-valve trans-catheter aortic valve replacement was considered. There were however several high-risk features and technically challenging aspects including low coronary ostia height, poor visualization of the aortic sinuses, and difficulty in identification of the coplanar view due to severe aortic insufficiency, and a highly mobile aortic valve mass. After meticulous peri-procedural planning, trans-catheter aortic valve replacement was carried out with a SAPIEN 3 balloon-expandable valve without any complication. Strategies undertaken to navigate the technically challenging aspects of the case are discussed.

Late Paravalvular Aortic Regurgitation: Migration of the Valve or Late Recoil?

A 79-year-old man underwent trans-catheter aortic valve replacement for symptomatic severe aortic stenosis with a 26-mm Edwards SAPIEN XT valve. Immediately after valve deployment there was moderate amount of paravalvular leak. Post-dilation was performed with an additional 2 cc of volume, and the paravalvular leak was reduced to trace. Nine months later, trans-thoracic echocardiography revealed moderate to severe paravalvular leak and possible aortic migration of the valve. The patient was brought back for the treatment of the paravalvular leak which was suspected to be due to valve migration. However, fluoroscopy and trans-esophageal echocardiography showed good valve position. Measurement of late valve recoil in the Coplanar view using cine-angiographic analysis software showed that the lower third of the valve had the greatest late recoil (-1.74 mm, 6.55%), which presumably accounted for the progression of the paravalvular leak. Valve-in-valve trans-catheter aortic valve replacement was performed with a 26-mm SAPIEN 3 valve and the paravalvular leak was reduced to trace. This case displays late recoil as a likely mechanism for development of paravalvular leak after SAPIEN XT valve implantation. Our case illustrates that late recoil needs to be systematically evaluated in future studies, especially when trans-catheter aortic valve replacement is being expanded to lower risk and younger patients for whom the longevity and long-term performance of these valves is of critical importance.

A case of isolated renal involvement of polyarteritis nodosa successfully treated with steroid monotherapy.

Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis that affects medium-sized and small-sized arteries. The spectrum of disease ranges from involving a single organ to polyvisceral failure. We report a case of a 75-year-old male presented with solely hypertension and mild renal function impairment as a consequence of diffuse renal necrotising vasculitis with occlusive but non-stenotic lesions associated with PAN. The overall prognosis of PAN has been improved in recent decades, primarily reflecting early diagnosis and more effective treatments. Therefore, early diagnosis is critical and it warrants full investigations even in those patients without obvious multiorgan manifestations. In those instances, with mild disease, steroid monotherapy has been shown to be effective with excellent response. Our patient responded well to steroid monotherapy and we were able to gauge his response by improvement in his blood pressure.

Acute Kidney Injury After Transcatheter Aortic Valve Replacement.

BACKGROUND: Acute kidney injury (AKI) during transcatheter aortic valve replacement (TAVR) increases morbidity and mortality. In this study, we investigated the incidence and risk factors for AKI in patients undergoing TAVR. METHODS: Two hundred ninety consecutive patients underwent TAVR. Valve Academic Research Consortium (VARC)-I criteria for AKI diagnosis at 72 hours, and VARC-II criteria at seven days were employed. RESULTS: Overall AKI incidence was 24.62% (65/264): 50 patients at 72 hours and 15 patients at seven days. Multivariate logistic regression determined transapical (TA) approach (OR: 4.46 [1.37-7.63]), preprocedural glomerular filtration rate less than 45 mL/min (OR: 3.47 [1.35-14.70]), and blood transfusion (OR: 3.34 [1.58-11.09]) as independent predictors for AKI at 72 hours; and prior coronary artery bypass grafting (OR: 3.02 [1.007-9.09]) and peripheral artery disease (PAD) (OR: 3.53 [1.06-11.62]) for AKI at seven days. In-hospital and 30-day mortality was higher in AKI patients. Non-AKI patients' survival was 93% at six months, 89% at 12 months, and 86% at 24 months, whereas survival in AKI at 72 hours was 66% at 6, 12, and 24 months (HR AKI vs. non-AKI: 3.9 [CI: 2.0-7.6]), and survival in AKI at seven days was 64% at 6, 12, and 24 months, HR: 3.13 (CI: 1.42-6.92). For the 12 dialysis patients survival was 82% at 6, 12, and 24 months. CONCLUSIONS: AKI after TAVR is associated with worse outcomes. Blood transfusion should be administered restrictively in TAVR. Patients with CKD, PAD, prior CABG, and TA approach require close surveillance as they are at risk for AKI through seven days after TAVR. doi: 10.1111/jocs.12768 (J Card Surg 2016;31:416-422).

Extracorporeal ultrafiltration therapy for acute decompensated heart failure.

Congestion is the most common reason for hospitalization of patients with acute decompensated heart failure (ADHF) and adversely impacts their outcomes. Extracorporeal ultrafiltration (UF) therapy has re-emerged as an effective strategy for decongestion in this setting. This article is intended to discuss key concepts in UF and its technique, provide a brief historical view of UF application for decongestion in ADHF, review the hemodynamic and neurohormonal effects of UF and their positive effects on the pathophysiology of ADHF, discuss the findings of the landmark trials in this field, and explain key findings of these studies as well as the apparent discrepancies in their findings. In a separate section we discuss the intricacies of renal dysfunction in ADHF as it plays a very important role in understanding the current evidence and designing futures clinical trials of UF in ADHF. In the end, the authors provide their perspective on the future role of UF in management of patients with ADHF and congestion.

Uric acid and the prediction models of tumor lysis syndrome in AML.

We investigated the ability of serum uric acid (SUA) to predict laboratory tumor lysis syndrome (LTLS) and compared it to common laboratory variables, cytogenetic profiles, tumor markers and prediction models in acute myeloid leukemia patients. In this retrospective study patients were risk-stratified for LTLS based on SUA cut-off values and the discrimination ability was compared to current prediction models. The incidences of LTLS were 17.8%, 21% and 62.5% in the low, intermediate and high-risk groups, respectively. SUA was an independent predictor of LTLS (adjusted OR 1.12, CI95% 1.0-1.3, p = 0.048). The discriminatory ability of SUA, per ROC curves, to predict LTLS was superior to LDH, cytogenetic profile, tumor markers and the combined model but not to WBC (AUCWBC 0.679). However, in comparisons between high-risk SUA and high-risk WBC, SUA had superior discriminatory capability than WBC (AUCSUA 0.664 vs. AUCWBC 0.520; p <0.001). SUA also demonstrated better performance than the prediction models (high-risk SUAAUC 0.695, p<0.001). In direct comparison of high-risk groups, SUA again demonstrated superior performance than the prediction models (high-risk SUAAUC 0.668, p = 0.001) in predicting LTLS, approaching that of the combined model (AUC 0.685, p<0.001). In conclusion, SUA alone is comparable and highly predictive for LTLS than other prediction models.