Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles.

The dietary approach to stop hypertension (DASH) diet combines the antihypertensive effect of a low sodium and high potassium diet. In particular, the potassium component of the diet acts as a switch in the distal convoluted tubule to reduce sodium reabsorption, similar to a diuretic but without the side effects. Previous trials to understand the mechanism of the DASH diet were based on animal models and did not characterize changes in human ion channel protein abundance. More recently, protein cargo of urinary extracellular vesicles (uEVs) has been shown to mirror tissue content and physiological changes within the kidney. We designed an inpatient open label nutritional study transitioning hypertensive volunteers from an American style diet to DASH diet to examine physiological changes in adults with stage 1 hypertension otherwise untreated (Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. N Engl J Med 344: 3-10, 2001). Urine samples from this study were used for proteomic characterization of a large range of pure uEVs (small to large) to reveal kidney epithelium changes in response to the DASH diet. These samples were collected from nine volunteers at three time points, and mass spectrometry identified 1,800 proteins from all 27 samples. We demonstrated an increase in total SLC12A3 [sodium-chloride cotransporter (NCC)] abundance and a decrease in aquaporin-2 (AQP2) in uEVs with this mass spectrometry analysis, immunoblotting revealed a significant increase in the proportion of activated (phosphorylated) NCC to total NCC and a decrease in AQP2 from day 5 to day 11. This data demonstrates that the human kidney's response to nutritional interventions may be captured noninvasively by uEV protein abundance changes. Future studies need to confirm these findings in a larger cohort and focus on which factor drove the changes in NCC and AQP2, to which degree NCC and AQP2 contributed to the antihypertensive effect and address if some uEVs function also as a waste pathway for functionally inactive proteins rather than mirroring protein changes.NEW & NOTEWORTHY Numerous studies link DASH diet to lower blood pressure, but its mechanism is unclear. Urinary extracellular vesicles (uEVs) offer noninvasive insights, potentially replacing tissue sampling. Transitioning to DASH diet alters kidney transporters in our stage 1 hypertension cohort: AQP2 decreases, NCC increases in uEVs. This aligns with increased urine volume, reduced sodium reabsorption, and blood pressure decline. Our data highlight uEV protein changes as diet markers, suggesting some uEVs may function as waste pathways. We analyzed larger EVs alongside small EVs, and NCC in immunoblots across its molecular weight range.

Postoperative Fluid Accumulation is Associated With Underestimation of AKI Severity in Lung Transplant Recipients.

BACKGROUND: Post-lung transplantation (LTx) fluid accumulation can lead to dilution of serum creatinine (SCr). We hypothesized that fluid accumulation might impact the diagnosis, staging, and outcome of posttransplant acute kidney injury (AKI). METHODS: In this retrospective study, we analyzed data from 131 adult LTx patients at a single German lung center between 2005 and 2018. We assessed the occurrence of AKI within 7 days posttransplant, both before and after SCr-adjustment for fluid balance (FB), and investigated its impact on all-cause mortality. Transient and persistent AKIs were defined as return to baseline kidney function or continuation of AKI beyond 72 h of onset, respectively. RESULTS: AKI was diagnosed in 58.8% of patients according to crude SCr values. When considering FB-adjusted SCr values, AKI severity was underestimated in 20.6% of patients, that is, AKI was detected in an additional 6.9% of patients and led to AKI upstaging in 23.4% of cases. Patients initially underestimated but detected with AKI only after FB adjustment had higher mortality compared to those who did not meet AKI criteria (hazard ratio [HR] 2.98; 95% confidence interval [CI] 1.06, 8.36; p = 0.038). Persistent AKI was associated with higher mortality than transient AKI, regardless of using crude or adjusted SCr values (p < 0.05). Persistent AKI emerged as an independent risk factor for mortality (HR 2.35; 95% CI 1.29, 4.30; p = 0.005). CONCLUSION: Adjusting for FB and evaluating renal recovery patterns post-AKI may enhance the sensitivity of AKI detection. This approach could help identify patients with poor prognosis and potentially improve outcomes in lung transplant recipients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03039959, NCT03046277.

Pulmonary malakoplakia secondary to Rhodococcus equi infection mimicking a lung neoplasm in a lung transplant recipient.

Pulmonary masses occasionally occur after lung transplantation and vary in etiology, which includes malignant and benign conditions, such as infection. Here, we report a case of a patient presenting with a lung mass 3 years after lung transplant. To our knowledge, this is the first described case of pulmonary malakoplakia due to Rhodococcus equi infection in an allograft post-lung transplantation. This case outlines the challenges of differentiating benign from malignant masses after transplantation.

Extracellular Vesicles in Acute Kidney Injury.

Extracellular vesicles (EVs) are promising novel cellular communicators and biomarkers in acute kidney injury (AKI). These submicron vesicles derive from all cell types along the urinary tract and reflect molecular processes of their parent cells and physiological and pathological conditions in AKI. Several EV protein and RNA biomarker candidates have been identified. They have shown to differentiate AKI etiology and pinpoint to disease mechanisms. In fact, EV research has opened up a new frontier of biomarker discovery since some less abundant biomarkers are concentrated in EVs, which makes them more easily detectable. EVs are also functional and are involved in intra-nephron communication. Tubular-interstitial communication is current focus in EV research in AKI as it can help to understand maladaptive processes in AKI. EVs are also promising therapeutic tools and have been shown to be regenerative in many different models of AKI. Rigorous studies are needed to validate these findings, and more sensitive EV detection and characterization tools need to be developed to dissect EV biology in renal disease and AKI.

Pulmonary disorders in athletes.

Exercise is rarely limited by pulmonary causes in normal individuals. Cardiac output and peripheral muscle disease are usually the limiting factors. Although minute ventilation rises steeply during exercise, normal individuals maintain a substantial breathing reserve. Exercise in patients, however, can be limited by pulmonary disorders. Acute pulmonary causes (exercise-induced bronchospasm, vocal cord dysfunction, exercise-induced anaphylaxis, and exercise-induced urticaria) or chronic disorders (obstructive and restrictive lung disorders) reduce exercise tolerance. Exercise testing has proved the mainstay for diagnosis and treatment of these disorders.

Role of bronchodilators in chronic obstructive pulmonary disease.

The prevalence of chronic obstructive pulmonary disease (COPD) continues to be on the rise. Bronchodilators are first line agents for the symptomatic management of this disease and have proven to be effective in both stable disease status and exacerbations. The stepwise escalation of therapy for COPD according to severity has been outlined in international guidelines. Different classes of bronchodilators exist. The most experience is available for short-acting beta-agonists and anticholinergics. These agents are mainly recommended for the treatment of mild COPD and for symptomatic patients on an as needed basis. Long-acting beta-agonists and anticholinergics have been developed more recently. They are more convenient to use for patients with advanced disease who require maintenance therapy with bronchodilators, and have been shown in this group of patients to provide superior efficacy compared with short-acting agents. Tiotropium, a long-acting anticholinergic, appears to be particularly powerful and may eventually replace ipratropium as the primary agent for COPD treatment. In contrast, the usage of theophylline, which used to be part of the mainstay of treatment for COPD, has declined, mainly secondary to a narrow therapeutic margin and side effects, but it is inexpensive and still has its role. New agents like phosphodiesterase-4-inhibitors are interesting substances that may become important adjuncts in COPD management, but there is limited experience so far. None of the bronchodilators have been shown to change outcome in COPD, but this issue is under active investigation.