Clinical Kidney Journal最新文献

Background: Renal biopsy plays a crucial role in diagnosing and assessing the severity of immunoglobulin A nephropathy (IgAN), despite being an invasive procedure with potential risk of failure. Our study focused on evaluating the capability of [¹⁸F]AlF-NOTA-FAPI-04 PET/CT in identifying the extent of pathological alterations in IgAN.

Methods: Twenty patients (13 males and 7 females; mean age, 44 ± 16 years) with newly diagnosed primary IgAN and 10 patients (7 males and 3 females; mean age, 51 ± 4 years) without known renal disease underwent [¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging. Kidney tissues from biopsies were stained with various techniques and examined using immunofluorescence. The Oxford classification was used to evaluate pathological indicators. Immunohistochemical staining was conducted to assess α-smooth muscle actin (αSMA) and fibroblast activation protein (FAP) expression. Renal FAPI uptake measured by positron emission tomography/computed tomography (PET/CT) (maximum and mean standardized uptake value, SUV_max and SUV_mean) was correlated with histological findings.

Results: The renal parenchymal FAPI uptake was significantly higher in IgAN patients compared with control patients (SUV_max = 3.9 ± 1.3 vs 1.9 ± 0.4, SUV_mean = 3.6 ± 1.2 vs 1.5 ± 0.4; all P < .001). We identified a significant difference in renal parenchymal FAPI uptake among the various categories of the Oxford classification. Correlation analysis revealed a positive association between SUV_max and interstitial fibrosis and tubular atrophy, as well as tubulointerstitial inflammation scores in scarred cortex and non-scarred cortex (r = 0.637, 0.593 and 0.491, all P < .05), Similar associations were observed between SUV_mean and these scores (r = 0.641, 0.592 and 0.479, all P < .05). Furthermore, significant positive correlations were observed between SUV_max or SUV_mean and the staining scores for glomerular αSMA and FAP, as well as for tubulointerstitial αSMA and FAP (all P < .01).

Conclusion: [¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging offers IgAN patients a non-invasive and reproducible auxiliary modality to monitor disease progression.

Background: Knowledge of which medications may lead to acute kidney injury (AKI) is limited, relying mostly on spontaneous reporting in pharmacovigilance systems. We here conducted an exploratory drug-wide association study (DWAS) to screen for associations between dispensed drugs and AKI risk.

Methods: Using two large Danish and Swedish data linkages, we identified AKI hospitalizations occurring between April 1997 and December 2021 in Denmark and between March 2007 and December 2021 in Sweden. We used a case-time control design comparing drug dispensing in the 3 months prior to the AKI with earlier periods for the same patient. Odds ratios (ORs) for the association between each drug and AKI were estimated using conditional logistic regression and adjusting for the presence of comorbidities. We sought replication of signals in both health systems and explored the plausibility of findings through pharmacovigilance system analysis in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, appearance in the RESCUE list of medications that report AKI as a side effect, PubMed evidence review and causality assessment through direct acyclic graphs.

Results: We included 20 622 adults in Denmark and 13 852 in Sweden hospitalized for AKI. In total, 16 unique medications were identified in both cohorts as associated to increased AKI occurrence. Of these, 10 medications had higher reporting ORs in the FAERS database, 9 were listed by RESCUE, and 7 appearing in PubMed. This analysis identified some medications with known AKI risks (i.e. likely true positives such as furosemide, penicillin, spironolactone and omeprazole), medications that may have initiated in response to conditions that lead to AKI (i.e. false positives like metoclopramide provided to treat nausea/vomiting) and other candidates (e.g. opioids) that warrant further evaluation in subsequent studies.

Conclusions: This hypothesis-generating study identifies medications with potential involvement in AKI that require confirmation and validation.

Background: Hypernatremia presents a common complication in intensive care unit (ICU) patients, associated with increased mortality and length of stay. This study investigates the effect of sodium chloride 0.9% compared with glucose 5% solution as the standard intravenous drug diluent on the prevalence of hypernatremia in a medical ICU.

Methods: This is a retrospective before-and-after study comparing two consecutive patient groups before and after the standard drug solvent was changed from sodium chloride 0.9% to glucose 5% solution for compatible medications. A total of 265 adult COVID-19 patients admitted between October 2020 and March 2021 to the study ICU were included, with 161 patients in the timeframe when sodium chloride 0.9% was employed as the standard drug solvent and 104 patients when glucose 5% was used. Routine sodium measurements from arterial and venous blood gases, along with heparinized lithium plasma, were analyzed. The daily sodium concentrations and the prevalence of severe hypernatremia (>150 mmol/l) were assessed during the first 8 days after ICU admission.

Results: Baseline characteristics were similar between the two groups. The cumulative volume of intravenous drug diluents was comparable. In the glucose 5% group, about half of the total drug diluent volume was glucose 5% [mean (SD): 2251.6 (2355.4) ml], compared to 135.0 (746.9) ml (P < .001) in the control group. Average sodium concentrations diverged after day two, with the glucose 5% group consistently showing lower sodium levels (mean difference of ∼2.5 mmol/l). Severe hypernatremia occurred less frequently in the glucose 5% group (6.6% vs. 20%).

Conclusion: Glucose 5% solution as the standard intravenous drug solvent significantly reduced sodium concentrations and the occurrence of severe hypernatremia. This simple modification in solvent choice may serve as a preventive strategy against hypernatremia in the ICU. Further prospective research is necessary to determine associated clinical outcomes.

Trial registration: The trial was registered in the German Clinical Trials Register (DRKS00031877).

Background: After the risk of drug-induced liver injury was detected during tolvaptan clinical development for the treatment of autosomal dominant polycystic kidney disease (ADPKD), a post-marketing pharmacovigilance study was required for European Union regulatory approval.

Methods: This is an interim analysis from a prospective, observational study enrolling patients prescribed tolvaptan for ADPKD in routine clinical practice. Data were obtained through physician records collected during regular care. Per the prescribing label, liver transaminases were to be monitored monthly for the first 18 months of treatment and once every 3 months thereafter. Patients and physicians were required to report adverse events suggestive of serious and potentially fatal liver injury. Data collection was from October 2016 to April 2022.

Results: Of 2074 patients (median follow-up 528 days), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 times the upper limit of normal (ULN) were reported in 75 (3.6%) patients. At data cut-off, the enzyme elevations were confirmed for 65 patients. Among the 65 confirmed patients, in addition to transaminase elevations, there were 69 adverse events suggestive of liver injury. Tolvaptan was interrupted or withdrawn in 59/65 (90.8%) participants with confirmed ALT or AST ≥3 times the ULN, with most transaminase elevations and adverse events resolved or resolving at data cut-off. No liver enzyme elevations met laboratory criteria for Hy's law cases.

Conclusions: Transaminase elevations occurred post-marketing in a similar proportion of patients as reported in clinical trials (4.4-5.6%). Regular monitoring per label facilitates prompt detection of liver adverse events and intervention to mitigate the risk of severe injury.

Background: Previously, a comprehensive review of the risk factors for unplanned dialysis initiation (UDI) was conducted by Hassan et al. (2019), based on studies published up to the end of 2017. They demonstrated that high-quality data and well-designed studies on the subject are lacking. Thus we updated their review to establish the modifiable factors associated with UDI.

Methods: MEDLINE and Embase were searched from January 2018 to August 2023. Following several rounds of screening, we identified 17 international studies (the majority of which were based in Europe) that met the eligibility criteria.

Results: Many of the included studies were well designed, utilised large datasets and adopted properly adjusted analyses to examine associations between patient characteristics and UDI. Definitions of UDI varied across studies, i.e. timeliness of presentation, vascular access type, initiating dialysis as an inpatient/outpatient or for life-threatening indications. The most common risk factors reported were cardiovascular disease, older age, lower body mass index, cause of kidney disease, cancer, diabetes, lower serum albumin, faster decline in kidney function and fewer number of nephrology visits prior to dialysis start. These were in line with those reported by Hassan et al., however, our updated review revealed several other important predictors of UDI, e.g. worse coding of chronic kidney disease in the general practitioner health record, lower health literacy and having acute kidney injury.

Conclusions: Our review provides new insights into reasons why people start dialysis in an unplanned manner, many of which are modifiable, thus contributing to efforts in reducing the rate of UDI.

Background: While SARS-CoV-2 infection has direct obvious consequences on patients undergoing dialysis, the COVID-19 pandemic also had an indirect impact on health systems. Therefore, we aimed to determine whether the COVID-19 era itself was associated with adverse consequences in the Swiss dialysis population as compared to the pre-COVID-19 era, while accounting for direct impact of SARS-CoV-2 infection.

Methods: We retrospectively included all patients recorded in the Swiss dialysis registry from January 2014 to December 2022. The pre-COVID-19 era and the COVID-19 era were defined based on the cut-off date of January 2020. Cox proportional hazard model was used with all-cause mortality as the primary outcome.

Results: The cohort consisted of 7837 patients from 97 dialysis centres. Median age was 68.6 years with 66.1% men. Crude mortality rates were 11.6% (11.0% to 12.2%) and 14.2% (13.4% to 14.9%) person-years for the pre-COVID-19 era and the COVID-19 era, respectively. In multivariable analysis, SARS-CoV-2 infection was associated with an increased risk of mortality (HR 4.26, 95% CI 3.65 to 4.97, P < .001) while the COVID-19 era itself was not (HR 0.98, 95% CI 0.88 to 1.08, P = .687).

Conclusions: The COVID-19 era was not associated with an excess of mortality in the Swiss dialysis population as compared to the pre-COVID-19 era when accounting for the direct effect of SARS-CoV-2 infection. This suggests that control measures established during the pandemic did not have a negative impact on dialysis patients at the national level. These results could inform health policy makers in the eventuality of future pandemics.

Background: Patients with cardiovascular disease (CVD), diabetes mellitus (DM) and chronic kidney disease (CKD) often experience fragmented care, which negatively impacts outcomes and health-related quality of life (HRQoL). This study assessed whether multidisciplinary, person-centred care at an integrated clinic improves clinical outcomes and HRQoL.

Methods: This prospective, open, blinded-endpoint trial (CareHND; NCT03362983) included 131 patients with CVD, DM and CKD stages 3-4, most of whom were enrolled during or shortly after acute hospitalization. The intervention group received person-centred care from cardiologists, nephrologists, endocrinologists and specialist nurses at an integrated clinic; the control group received traditional care from separate specialists. Primary disease progression outcome was the composite of major adverse renal and cardiovascular events (MARCE) including death, heart failure (HF) readmission, myocardial infarction, percutaneous coronary intervention/coronary artery bypass graft, acute or end-stage kidney failure, or transient ischaemic attack/stroke at 2 years. Co-primary person-centred outcomes was self-reported HRQoL by RAND-36.

Results: In a pre-specified interim analysis, patients randomized to integrated care had lower estimated glomerular filtration rate and higher NT-proBNP (N-terminal pro brain natriuretic peptide) than traditional care. Follow-up ranged from 2.0 to 5.7 years. Kaplan-Meier analysis showed no difference in MARCE between groups. Cox-regression adjusting for baseline differences, indicated a trend towards reduced HF hospitalizations for integrated care (hazard ratio 0.53; confidence interval 0.28-1.01; P = .054). Integrated care improved role physical and social function scores, and self-rated health (P = .021, P = .019 and P = .011, respectively).

Conclusions: Integrated care improved several dimensions of HRQoL but did not improve MARCE compared with traditional care in this small trial. We observed a trend towards reduced HF hospitalizations. Overall, integrated care presents a promising alternative.

Acute kidney injury (AKI) is a common syndrome in hospitalized patients and is associated with increased morbidity and mortality. The focus of AKI care requires a shift away from strictly supportive management of established injury to the early identification and timely prevention of worsening renal injury. Identifying patients at risk for developing or progression of severe AKI is crucial for improving patient outcomes, reducing the length of hospitalization and minimizing resource utilization. Implementation of dynamic risk scores and incorporation of novel biomarkers show promise for early detection and minimizing progression of AKI. Like any risk assessment tools, these require further external validation in a variety of clinical settings prior to widespread implementation. Additionally, alerts that may minimize exposure to a variety of nephrotoxic medications or prompt early nephrology consultation are shown to reduce the incidence and progression of AKI severity and enhance renal recovery. While dynamic risk scores and alerts are valuable, implementation requires thoughtfulness and should be used in conjunction with the overall clinical picture in certain situations, particularly when considering the initiation of fluid and diuretic administration or renal replacement therapy. Despite the contemporary challenges encountered with alert fatigue, implementing an alert-based bundle to improve AKI care is associated with improved outcomes, even when implementation is incomplete. Lastly, all alert-based interventions should be validated at an institutional level and assessed for their ability to improve institutionally relevant and clinically meaningful outcomes, reduce resource utilization and provide cost-effective interventions.

Background: To prevent loss of peritoneal function caused by persistent abdominal inflammation, the guidelines recommend early extubation in patients with refractory peritoneal dialysis (PD)-associated peritonitis (rPDAP). In attempt to pinpoint high-risk patient cohorts that did not respond to treatment for refractory peritonitis, we created a model to predict the effectiveness of peritonitis treatment.

Methods: This observational cohort study included PD patients from 1 January 2011 to 31 December 2020. Multivariate logistic regression analysis was used to explore the factors affecting the occurrence and prognosis of rPDAP, and to construct a predictive model for the success of rPDAP treatment. Receiver operator characteristic curve, calibration and decision curve were drawn to evaluate the predictive performance of the model.

Results: A total of 1397 cases of PDAP occurred in our center during the study period, of which 558 cases were diagnosed as rPDAP. The incidence of refractory peritonitis was 0.047 cases/patient-year. In the study, 440 cases with rPDAP were included. Among them, 304 cases (69.1%) had been successfully cured, while 136 cases (30.9%) were treatment failure, of which 19 cases (13.9%) died, 85 cases (62.5%) transferred to hemodialysis and 32 cases (23.5%) were relapse/recurrent peritonitis. Dialysate culture results showed 132 (30.0%) cases were infected with Gram-positive bacteria and 161 (36.6%) Gram-negative bacteria. Multivariate logistic regression analysis showed that episodes of peritonitis previously ≤3 times were correlated with the better prognosis of rPDAP, but white blood cell (WBC) counts in peritoneal dialysate on the third day of peritonitis or WBC counts on the fifth day ≥300 × 10⁶/L, the pathogenic microorganism with Gram-negative bacteria, as well as longer duration of PD were associated with poor outcomes. The C-statistical value of the training data set was 0.870 (95% confidence interval 0.821-0.918). The calibration curve and clinical decision-making curve also proved that this nomogram could accurately predict the success of treatment in patients with refractory peritonitis.

Conclusion: The nomogram model created through internal verification indicated a strong clinical application value and a high prognostic prediction accuracy for rPDAP.