American Journal of Nephrology最新文献

Introduction: Rural-living veterans with chronic kidney disease and refractory hypertension have a higher mortality rate and are hospitalized more frequently than veterans living in urban or suburban areas. They also face particularly unique challenges in accessing nephrology specialty care. Previous studies suggest virtual nephrology care can be used to increase access to care for veterans. The purpose of this study was to examine veteran's perceptions and experiences with a veteran administration (VA) virtual nephrology program.

Methods: We conducted semi-structured interviews with forty-four veterans at five rural VA medical centers who were receiving virtual nephrology care ("tele-nephrology").

Results: Four major themes arose that represent the veterans' perceptions and experiences with VA virtual nephrology care: (1) tele-nephrology provides timely access to care for veterans living in rural areas, (2) clinical partnerships between primary care and tele-nephrology are key to veterans' health, (3) veterans' technology fears were assuaged with virtual nephrology care, and (4) improvements to care include more direct access to virtual nephrologists.

Conclusion: This evaluation represents an important step forward in how the VA can enhance virtual nephrology care to better meet the needs of rural veterans receiving care at facilities without VA specialty providers. Prior to the Choice and MISSION Acts, veterans were often required to drive long distances to the closest VA specialty provider. However, since the COVID-19 pandemic, the VA has been shifting care from the community to the VA via virtual care. Further research should examine veterans' experiences with different modalities of nephrology care as well as experiences of demographically and geographically diverse veterans.

Introduction: Patients with chronic kidney disease (CKD) are at risk of medication therapy problems (MTPs) due to high comorbidity and medication burden. Using data from the Kidney Coordinated HeAlth Management Partnership (Kidney CHAMP) trial, we used machine learning to build a predictive model to identify MTP high-risk patients with CKD in the primary care setting.

Methods: We used baseline data from patients enrolled in the intervention arm of the Kidney CHAMP trial, completed May 2019-July 2022, which tested a population health management strategy, including medication management, for improving CKD care. The dataset was divided into 80% training and 20% testing subsets. The area under the ROC curve (AUROC) was used to assess classification accuracy in distinguishing between patients with and without MTP. Eight candidate models were considered, and the top three performing models (random forest, support vector machines, and gradient boosting), based on cross-validated AUROC on training data, underwent further refinement. The model with the highest AUROC in the testing set, while considering the bias/variance trade-off, was selected as the best-performing model. SHapley Additive exPlanations was then leveraged using the best-performing model to evaluate the impact of each predictor to the final risk score.

Results: Among 730 patients who received medication review at baseline, 566 (77.5%) had at least 1 MTP. Key demographics were mean age 74 years, 55% female, 92% white, 64% with diabetes, and the mean number of medications 5.8 at baseline. The random forest model had the best performance on the testing set with AUROC 0.72, sensitivity 0.80, and specificity 0.64. The five most influential variables, ranked in descending order of importance for predicting individuals with MTP, were diabetes status (yes/no), hemoglobin A1C (HbA1C), urine albumin-to-creatinine ratio (UACR), systolic blood pressure, and age.

Conclusion: In outpatient primary care, a machine learning-based MTP risk calculator that uses routinely available clinical data can identify patients with moderate-high-risk CKD who are at high risk for developing MTPs.

Background: Diabetic kidney disease (DKD) is a common chronic microvascular complication of diabetes, and the increasing number of patients with this condition imposes a great economic burden globally. The rapid development of biotechnology has revealed more in-depth pathogenic mechanisms related to the occurrence of DKD. Lots of studies have provided evidence that communication between various cell types, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular epithelial cells, plays an irreplaceable role in the development of DKD. Stem cells have the unique advantages of establishing adaptive communication with renal cells to alleviate the damage in DKD. In addition, some drugs can also affect cell communication in DKD.

Summary: This review presents a review of recent progress on renal cellular crosstalk in the pathogenesis of DKD, and the findings of the review may shed light on the development of a novel therapeutic approach from the perspective of cellular communication.

Key message: Cellular communication in DKD not only reveals the new pathogenic mechanisms but also provides potential therapeutic targets.

Introduction: The estimated glomerular filtration rate (eGFR) derived from either creatinine (eGFRcr) or cystatin C (eGFRcys) is common preoperative test in routine clinical practice. Recently, the difference between eGFRcys and eGFRcr (eGFRdiff) has been suggested to reflect health status and frailty. This study was aimed to determine the association of eGFRdiff with adverse events among adults undergoing major surgery.

Methods: We conducted a retrospective cohort study of adults undergoing major surgery from 19 academic healthcare centers across China from January 1, 2013, to December 31, 2020. The eGFRdiff was categorized based on previous studied, that is, negative eGFRdiff (<-15 mL/min/1.73 m2), midrange eGFRdiff (-15 to 15 mL/min/1.73 m2), and positive eGFRdiff (≥15 mL/min/1.73 m2). Multivariate logistic regression was performed to assess the association of eGFRdiff with 30-day mortality, 90-day mortality, admission to intensive care unit (ICU), and development of postoperative acute kidney injury (AKI) after surgery.

Results: Among 158,336 participants undergoing major surgery, the mean age was 57 years and 52.5% were male. The most frequent surgery type was general (47.5%), followed by the orthopedic (17.0%) and thoracic surgery (12.9%). The mean eGFRdiff was -7.6 mL/min/1.73 m2, negative (<-15 mL/min/1.73 m2) and positive (≥15 mL/min/1.73 m2) eGFRdiff values were observed in 36.1% and 11.6% participants, respectively. In multivariable analyses after adjustment for confounding factors, the negative eGFRdiff had OR of 1.34 (95% CI: 1.20-1.50) for 30-day mortality, 1.33 (95% CI: 1.23, 1.43) for 90-day mortality, 1.46 (95% CI: 1.41-1.50) for admission to ICU, and 1.39 (95% CI: 1.32-1.46) for postoperative AKI. Moreover, the positive eGFRdiff was associated lower risk of 90-days mortality, admission to ICU, and postoperative AKI.

Conclusions: Negative GFRdiff may be a valuable marker for identifying individuals at a higher risk of adverse events in participants undergoing major surgery.

Introduction: Patients with severe acute kidney injury (AKI) with associated acute hypoxemic respiratory failure (AHRF) experience poorer outcomes, including higher rates of in-hospital mortality, relative to patients with less severe AKI, or those without associated AHRF. Zegocractin is a calcium release-activated calcium (CRAC) channel inhibitor with potent anti-inflammatory and pulmonary endothelial protective properties. Preclinical and early phase clinical studies suggest that zegocractin may be an effective agent for the treatment of AKI.

Methods: KOURAGE (NCT06374797) is a multicenter, phase 2, randomized, double blind, placebo-controlled trial that aims to enroll approximately 150 patients with severe AKI and AHRF. Eligible patients will be randomized 1:1 to receive a total of five daily doses of zegocractin intravenous emulsion (Auxora™) or matching placebo. The objective was to evaluate the safety and efficacy of Auxora in patients with severe AKI, with the primary efficacy endpoint defined as the number of days alive, ventilator-free and kidney replacement therapy-free from the start of the first infusion of the study drug through day 30. A key secondary efficacy endpoint is the proportion of patients with major adverse kidney events at day 90.

Conclusion: The KOURAGE trial will investigate the safety and efficacy of Auxora in patients with severe AKI and AHRF.

Introduction: Serum concentrations of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) decline as chronic kidney disease (CKD) advances, becoming insufficient without effective vitamin D repletion and driving onset of secondary hyperparathyroidism (SHPT). Randomized controlled trials (RCTs) in non-dialysis CKD patients have established that extended-release calcifediol (ERC) effectively raises 25D and 1,25D and reduces elevated intact parathyroid hormone (iPTH) despite the progressive loss of renal cytochrome P450 25D-1α-hydroxylase (CYP27B1), suggesting its potential usefulness in treating SHPT in end-stage kidney disease (ESKD).

Methods: This pilot RCT explored the safety and efficacy of oral ERC to raise serum total 25D to ≥50 ng/mL, normalize circulating 1,25D, and reduce elevated iPTH in ESKD patients requiring regular hemodialysis (HD). Forty-four adults from 13 US clinics requiring HD three times per week were washed out from iPTH-lowering therapies and randomized 3:1 to 26 weeks of treatment with ERC (300 µg/HD) or placebo. Participants had a mean age of 56.4 ± 11.6 years, body mass index of 32.7 ± 8.1 kg/m2, 46% were female, 68% black, 30% white, and 24% Hispanic. At randomization, iPTH had to be 300 to <1,200 pg/mL, 25D <50 ng/mL, corrected serum calcium <9.8 mg/dL, and phosphorus <6.5 mg/dL. These parameters were monitored weekly or biweekly and 1,25D quarterly.

Results: Mean (±SE) serum total 25D rose with ERC treatment from 24.1 ± 1.7 ng/mL at baseline (BL) to steady-state levels of 157.7 ± 10.4 (p < 0.001) after 12 weeks, with all individual levels exceeding 50 ng/mL but varying inversely with body weight. Serum 25D levels declined with placebo treatment from 36.0 ± 5.3 to 30.6 ± 5.5 ng/mL. Mean 1,25D rose from 9.4 ± 1.2 to 50.7 ± 7.8 pg/mL (p < 0.001) with ERC and concentrations surpassed 19.9 pg/mL (lower limit of normal) in 93% of participants. Mean iPTH increased 19.8 ± 10.6% from BL with placebo (497.6 ± 69.2 to 593.1 ± 95.1 pg/mL) but decreased 1.7 ± 4.7% (p < 0.05) with ERC (530.4 ± 29.4 to 529.6 ± 43.7 pg/mL). A strong correlation was observed with ERC treatment between serum 1,25D and 25D (R2 = 0.8248; p < 0.001) indicating that, on average, 1,25D normalized as 25D reached ≥50 ng/mL. Increases in mean serum calcium or phosphorus, episodes of hypercalcemia, or treatment-emergent adverse events were not observed with ERC treatment.

Conclusion: ERC safely raised serum total 25D, normalized low serum 1,25D, and stabilized elevated plasma iPTH in this pilot placebo-controlled RCT involving ESKD patients requiring regular HD. The observed increases in 1,25D indicated that ERC restored adequate endogenous vitamin D hormone production via substrate-driven conversion to calcitriol in extrarenal tissues expressing CYP27B1, thereby preventing further SHPT progression.

Introduction: Guidelines recommend that patients with a self-reported history of kidney stones or stones on imaging during living kidney donor (LKD) evaluation undergo 24-h urine stone risk testing. We examined eligibility decisions for LKD candidates at two high-volume academic transplant centers based on 24-h urine testing and imaging findings.

Methods: We identified potential LKDs with a self-reported history of kidney stones or stones identified on imaging, who underwent 24-h urine collection. Patients who could not donate due to other medical conditions were excluded. Differences in characteristics of patients approved versus rejected for donation were determined using t tests and chi-square tests, or nonparametric tests when appropriate.

Results: In total, 105 candidates met study criteria, of whom 22 (21%) were rejected for donation. Candidates rejected for donation had higher urinary calcium excretion (p < 0.001), supersaturation of calcium oxalate (p < 0.001), and supersaturation of calcium phosphate (p = 0.02). Thirty-four candidates repeated 24-h urine analyses following dietary or medical interventions for stone prevention. Candidates approved for donation had an increase in urinary volume (p = 0.045), reduction in urinary calcium excretion (p = 0.02), reduction in urinary oxalate excretion (p = 0.04), and reduction in supersaturations of calcium oxalate (p < 0.001), calcium phosphate (p = 0.004), and uric acid (p = 0.004). Those rejected for donation had no statistically significant changes in urinary parameters. While those rejected for donation had more stones on imaging compared to those approved, this did not reach statistical significance (p = 0.06).

Conclusion: Overall, urinary risk factors for nephrolithiasis and improvement in them following dietary or medical management were associated with approval for donation.

Introduction: Vaccination rates for influenza and COVID-19 remain low among people with chronic kidney disease (CKD). Nephrology care offers an opportunity to boost vaccination rates. Understanding provider perceptions can be key to developing effective intervention programs.

Methods: We conducted a nationwide survey among nephrology care providers. In a questionnaire, we assessed the providers' agreement with potential barriers to recommending influenza and COVID-19 vaccines and perceptions of selected vaccination programs on their acceptability, appropriateness, and feasibility.

Results: Between February and June 2023, 312 providers responded to the survey. Most providers agreed that there is sufficient evidence for influenza vaccines (270/311, 86.8%) and that vaccines reduce the risk of serious complications of influenza (277/310, 89.4%). However, 40/312 (12.8%) felt that recommending influenza vaccines is less important than other issues they must address. By profession, more physicians agreed with the evidence (112/123 or 91.1% vs. 39/49 or 79.5% for NPs and 83/101 or 82.2% for RNs, p = 0.007) than nurse practitioners (NPs) or nurses (RNs). The most perceived barrier was lack of self-efficacy: 95/311 (30.5%) felt that many patients will not get vaccinated even if they recommend it. Similar responses were seen for COVID-19 vaccines. Regarding vaccination programs, 209/235 (88.9%), 197/224 (87.9%), and 183/222 (82.4%) providers considered provider reminders acceptable, appropriate, and feasible. 209/239 (87.4%), 198/226 (87.6%), and 187/224 (83.5%) did so for standing orders. Onsite/walk-in vaccinations were viewed as acceptable by 192/242 (79.3%) but less feasible (137/222 or 61.7%). Fewer than 33% of providers perceived patient incentives as acceptable, appropriate, or feasible.

Conclusions: Most nephrology care providers believe that influenza and COVID-19 vaccinations offer evidence-based benefits, with slightly higher belief among physicians compared to NPs or RNs. However, important barriers to vaccination remain. Standing orders, provider reminders, and onsite/walk-in vaccination are favorably perceived by providers.

Introduction: Rituximab has become the first-line therapy for patients with membranous nephropathy (MN). However, approximately 30-40% of patients with MN do not respond to rituximab. We presented our single-center experience of treating rituximab-refractory MN with obinutuzumab which is a humanized and glycoengineered type II anti-CD20 monoclonal antibody.

Methods: Seventeen patients with rituximab-refractory phospholipase A2 receptor (PLA2R)-associated MN who received obinutuzumab at the First Affiliated Hospital of Xi'an Jiaotong University were included in this case series study. Clinical and laboratory parameters were evaluated at presentation, before and after obinutuzumab administration.

Results: Of all patients with an average age of 49.7 ± 13.7 years, 11 (64.7%) patients were men. The median disease duration was 12 (12, 42) months. At presentation, the proteinuria and serum albumin levels were 7.51 ± 3.55 g/day and 22.1 ± 3.6 g/L, respectively. The mean estimated glomerular filtration rate level was 103.5 ± 12.9 mL/min/1.73 m2, and the patients had a baseline anti-PLA2R level of 183.2 ± 92.9 RU/mL. At obinutuzumab administration, proteinuria and albumin levels were still consistent with nephrotic syndrome. After a median follow-up of 12.6 ± 5.0 months, complete remission was achieved in 9 (52.9%) and partial remission was achieved in 6 (41.2%) cases. Of the patients who achieved remission, the median remission time was 4.4 (4.0, 6.0) months. At 6 months, 12 (70.6%) patients achieved remission and 11 of 12 patients with available PLA2R measurements reached immunological remission.

Conclusion: Obinutuzumab may represent an attractive alternative therapy in rituximab-refractory patients. Larger prospective studies are needed to validate these findings.