COVID-19 Computed tomography patterns in renal replacement therapy patients / Padrões de tomografia computadorizada da COVID-19 em pacientes em terapia renal substitutiva

ABSTRACT Introduction: Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19. Methods: ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients. Results: We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002). Conclusions: In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

RESUMO Introdução: Doenças pulmonares são comuns em pacientes com doença renal em estágio terminal (DRET), dificultando o diagnóstico diferencial com COVID-19. Este estudo descreve achados de tomografia computadorizada de tórax (TC) em pacientes com DRET em terapia renal substitutiva (TRS) hospitalizados com suspeita de COVID-19. Métodos: Indivíduos maiores de 18 anos com DRET, encaminhados ao pronto-socorro com suspeita de COVID-19 foram incluídos. Dados clínicos e epidemiológicos foram extraídos de registros eletrônicos de saúde. A TC foi classificada como típica, indeterminada, atípica, negativa. Comparamos achados tomográficos de pacientes com COVID-19 positivos e negativos. Resultados: Recrutamos 109 pacientes (62,3% COVID-19-positivos) entre março e dezembro de 2020, idade média de 60 ± 12,5 anos, 43% mulheres. A etiologia mais comum da DRET foi diabetes. Tempo médio em diálise foi 36 meses, intervalo interquartil = 12-84. A lesão pulmonar mais comum foi opacidades em vidro fosco. O padrão típico de TC foi mais comum em pacientes com COVID-19 (40 (61%) vs. 0 (0%) em pacientes sem COVID-19, p < 0,001). Sensibilidade 60,61% (40/66), especificidade 100% (40/40). Valores preditivos positivos e negativos foram 100% e 62,3%, respectivamente. Padrão atípico de TC foi mais frequente em pacientes COVID-19-negativos (9 (14%) vs. 24 (56%) em COVID-19-positivos, p < 0,001), enquanto padrão indeterminado foi semelhante em ambos os grupos (13 (20%) vs. 6 (14%), p = 0,606), e padrão negativo foi mais comum em pacientes COVID-19-negativos (4 (6%) vs. 12 (28%), p = 0,002). Conclusões: Em pacientes com DRET em TRS hospitalizados, um padrão atípico de TC de tórax não pode excluir adequadamente o diagnóstico de COVID-19.

Renin–angiotensin–aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de enfermedad renal crónica en pacientes hipertensos añosos sin proteinuria: ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos

Introduction: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Materials and methods: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3–4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was −4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusions: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023). (AU)

Introducción: Actualmente no existe suficiente evidencia sobre el efecto nefroprotector de los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) en pacientes añosos con enfermedad renal crónica (ERC) sin proteinuria y sin cardiopatía. El objetivo es evaluar el efecto de los BSRAA en la progresión de la ERC en este grupo poblacional. Métodos: Se trata de un estudio prospectivo, aleatorizado, que compara la eficacia de los BSRAA vs. otros tratamientos antihipertensivos en la progresión renal en personas mayores de 65 años con ERC estadios 3 y 4 e índice albúmina/creatinina<30mg/g. Aleatorización 1:1 BSRAA o tratamiento antihipertensivo estándar. Se recogieron cifras tensionales y parámetros analíticos de un año previo a la aleatorización y durante el seguimiento. Resultados: Se incluyeron 88 pacientes seguidos durante tres años con edad media de 77,9±6,1 años. De estos, se aleatorizaron 40 al grupo BSRAA y 48 al estándar. La etiología de ERC fue: 53 vascular, 16 intersticial y 19 no filiada. En el primer grupo se observó una progresión de la ERC con una caída del filtrado glomerular estimado (FGe) de -4,3±1,1mL/min, mientras que en el grupo estándar un aumento del FGe durante el seguimiento de 4,6±0,4mL/min, p=0,024. No se apreciaron diferencias entre ambos en el control tensional, el número de antihipertensivos, la albuminuria, los niveles de potasio, la incidencia de eventos cardiovasculares ni la mortalidad durante el seguimiento. Conclusiones: En pacientes añosos no diabéticos con ERC no proteinúrica y sin cardiopatía el uso de BSRAA no añade beneficio en la progresión de la ERC. Ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos (PROERCAN) (NCT03195023). (AU)

Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

Remote Symptom Monitoring Using Patient-Reported Outcomes in Patients With Chronic Kidney Disease: Process Evaluation of a Randomized Controlled Trial.

BACKGROUND: In Denmark, outpatient follow-up for patients with chronic kidney disease (CKD) is changing from in-hospital visits toward more remote health care delivery. The nonuse of remote patient-reported outcomes (PROs) is a well-known challenge, and it can be difficult to explain which mechanisms of interventions influence the outcome. Process evaluation may, therefore, be used to answer important questions on how and why interventions work, aiming to enhance the implications for clinical practice. OBJECTIVE: This study aimed to provide insight into the intervention process by evaluating (1) the representativity of the study population, (2) patient and physician use patterns, (3) patient adherence to the intervention, and (4) clinical engagement. METHODS: A process evaluation determining the reach, dose, fidelity, and clinical engagement was carried out, alongside a multicenter randomized controlled trial (RCT). We developed and implemented an intervention using PRO measures to monitor outpatients remotely. Data were collected for the PRO intervention arms in the RCT from 4 sources: (1) PRO data from the participants to determine personal factors, (2) the web-based PRO system to identify key usage intervention patterns, (3) medical records to identify clinical factors relating to the use of the intervention, and (4) semistructured interviews conducted with involved physicians. RESULTS: Of the 320 patients invited, 152 (47.5%) accepted to participate. The study population reflected the target population. The mean adherence rate to the PRO intervention arms was 82% (95% CI 76-87). The questionnaire response rate was 539/544 (99.1%). A minority of 13 (12.9%) of 101 patients needed assistance to complete study procedures. Physicians assessed 477/539 (88.5%) of the questionnaires. Contact was established in 417/539 (77.4%) of the cases, and 122/539 (22.6%) of the patients did not have contact. Physicians initiated 288/417 (69.1%) and patients requested 129/417 (30.9%) of all the contacts. The primary causes of contact were clinical data (242/417, 58%), PRO data (92/417, 22.1%), and medication concerns and precautionary reasons (83/417, 19.9%). Physicians found the use of PRO measures in remote follow-up beneficial for assessing the patient's health. The inclusion of self-reported clinical data in the questionnaire motivated physicians to assess patient responses. However, some barriers were emphasized, such as loss of a personal relationship with the patient and the risk of missing important symptoms in the absence of a face-to-face assessment. CONCLUSIONS: This study demonstrates the importance and practical use of remote monitoring among patients with CKD. Overall, the intervention was implemented as intended. We observed high patient adherence rates, and the physicians managed most questionnaires. Some physicians worried that distance from the patients made it unfeasible to use their "clinical glance," posing a potential risk of overlooking crucial patients' symptoms. These findings underscore key considerations for the implementation of remote follow-up. Introducing a hybrid approach combining remote and face-to-face consultations may address these concerns. TRIAL REGISTRATION: ClinicalTrials.gov NCT03847766; https://clinicaltrials.gov/study/NCT03847766.

Renal artery coil embolization as an endovascular approach for establishing a rabbit model of chronic kidney disease.

PURPOSE: This study aimed to investigate the safety and feasibility of renal artery coil embolization for establishing chronic kidney disease (CKD) in rabbits. METHODS: Ten male adult New Zealand rabbits underwent renal artery coil embolization. Initially, the main renal artery on one side was completely embolized, followed by embolization of approximately 2/3 of the primary branches of the contralateral renal artery one week later. Four rabbits were randomly chosen for sacrifice at 4 weeks post-embolization, while the remaining six were sacrificed at 8 weeks post-embolization. The assessment encompassed the animals' general condition, angiography, biochemical parameters, inflammatory markers, and histopathological examination of the kidneys and hearts. RESULTS: Four weeks after embolization, serum creatinine level showed a significant increase (2.4 mg/dL ± 0.6, p = 0.009 vs. baseline), with a subsequent 4.12-fold elevation at 8 weeks post-embolization (4.9 mg/dL ± 1.4, p < 0.001 vs. baseline). Additionally, significant increases in serum blood urea nitrogen, calcium, and potassium ions were observed at 8 weeks post-embolization (58.3 mg/dL ± 19.0, p < 0.001 vs. baseline; 23.1 mg/dL ± 4.4, p < 0.001 vs. baseline; 6.3 mEq/L ± 0.7, p < 0.001 vs. baseline). The completely embolized kidney exhibited notable atrophy, severe fibrosis, and cortical calcification, whereas the contralateral partially embolized kidney displayed compensatory hypertrophy, along with glomerulosclerosis, tubular dilation, tubular casts, and interstitial fibrosis. CONCLUSION: Renal artery coil embolization proved effective and safe for establishing a CKD model in rabbits.

Interactive exploration of adverse events and multimorbidity in CKD.

BACKGROUND AND HYPOTHESIS: Persons with chronic kidney disease (CKD) are at increased risk of adverse events, early mortality, and multimorbidity. A detailed overview of adverse event types and rates from a large CKD cohort under regular nephrological care is missing. We generated an interactive tool to enable exploration of adverse events and their combinations in the prospective, observational German CKD (GCKD) study. METHODS: The GCKD study enrolled 5217 participants under regular nephrological care with an estimated glomerular filtration rate of 30-60 or >60 mL/min/1.73m2 and an overt proteinuria. Cardio-, cerebro- and peripheral vascular, kidney, infection, and cancer events, as well as deaths were adjudicated following a standard operation procedure. We summarized these time-to-event data points for exploration in interactive graphs within an R shiny app. Multivariable adjusted Cox models for time to first event were fitted. Cumulative incidence functions, Kaplan-Meier curves and intersection plots were used to display main adverse events and their combinations by sex and CKD etiology. RESULTS: Over a median of 6.5 years, 10 271 events occurred in total and 680 participants (13.0%) died while 2947 participants (56.5%) experienced any event. The new publicly available interactive platform enables readers to scrutinize adverse events and their combinations as well as mortality trends as a gateway to better understand multimorbidity in CKD: incident rates per 1000 patient-years varied by event type, CKD etiology, and baseline characteristics. Incidence rates for the most frequent events and their recurrence were 113.6 (cardiovascular), 75.0 (kidney), and 66.0 (infection). Participants with diabetic kidney disease and men were more prone to experiencing events. CONCLUSION: This comprehensive explorative tool to visualize adverse events (https://gckd.diz.uk-erlangen.de/), their combination, mortality, and multimorbidity among persons with CKD may manifest as a valuable resource for patient care, identification of high-risk groups, health services, and public health policy planning.

FHL2 in arterial medial calcification in chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Arterial medial calcification (AMC) is a common complication in individuals with chronic kidney disease (CKD), which can lead to cardiovascular morbidity and mortality. The progression of AMC is controlled by a key transcription factor called runt-related transcription factor 2 (RUNX2), which induces vascular smooth muscle cells (VSMCs) transdifferentiation into a osteogenic phenotype. However, RUNX2 has not been targeted for therapy due to its essential role in bone development. The objective of our study was to discover a RUNX2 coactivator that is highly expressed in arterial VSMCs as a potential therapy for AMC. METHODS: We employed transcriptomic analysis of human data and an animal reporter system to pinpoint FHL2 as a potential target. Subsequently, we investigated the mRNA and protein expression patterns of FHL2 in the aortas of both human and animal subjects with CKD. To examine the role of FHL2 in the RUNX2 transcription machinery, we conducted coimmunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) experiments. Next, we manipulated FHL2 expression in cultured VSMCs to examine its impact on high phosphate-induced transdifferentiation. Finally, we employed FHL2 null mice to confirm the role of FHL2 in the development of AMC in vivo. RESULTS: Among all the potential RUNX2 cofactor, FHL2 displays selective expression within the cardiovascular system. In the context of CKD subjects, FHL2 undergoes upregulation and translocation from the cytosol to the nucleus of arterial VSMCs. Once in the nucleus, FHL2 interacts structurally and functionally with RUNX2, acting as a coactivator of RUNX2. Notably, the inhibition of FHL2 expression averts transdifferentiation of VSMCs into an osteogenic phenotype and mitigates aortic calcification in uremic animals, without causing any detrimental effects on the skeletal system. CONCLUSION: These observations provide evidence that FHL2 is a promising target for treating arterial calcification in patients with CKD.

Perioperative Risk Factors of Acute Kidney Injury After Heart Transplantation and One-Year Clinical Outcomes: A Retrospective Cohort Study.

OBJECTIVES: This study aimed to identify perioperative risk factors of acute kidney injury after heart transplantation and to evaluate 1-year clinical outcomes. DESIGN: A retrospective single-center cohort study. SETTING: At a university hospital. PARTICIPANTS: All patients who underwent heart transplantation from January 2015 to December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors recorded acute kidney injury after heart transplantation. One-year mortality and renal function also were recorded. Risk factors of acute kidney injury were evaluated using a multivariate logistic regression model. Long-term survival was compared between patients developing acute kidney injury and those who did not, using a log-rank test. Among 209 patients included in this study, 134 patients (64% [95% CI (58; 71)]) developed posttransplantation acute kidney injury. Factors independently associated with acute kidney injury were high body mass index (odds ratio [OR]: 1.18 [1.02-1.38] per kg/m2; p = 0.030), prolonged duration of cold ischemic period (OR: 1.11 [1.01-1.24] per 10 minutes; p = 0.039), and high dose of intraoperative dobutamine support (OR: 1.24 [1.06-1.46] per µg/kg/min; p = 0.008). At 1 year, patients who developed postoperative acute kidney injury had higher mortality rates (20% v 8%, p = 0.015). Among 172 survivors at 1 year, 82 survivors (48%) had worsened their renal function compared with preheart transplantation. CONCLUSIONS: This study highlighted the high incidence of acute kidney injury after heart transplantation and its impact on patient outcomes. Risk factors such as body mass index, prolonged cold ischemic period duration, and level of inotropic support with dobutamine were identified, providing insights for preventive strategies.

Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. METHODS: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02-1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12-1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42-2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52-3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532. CONCLUSIONS: Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.

Comparison between beta-blockers and calcium channel blockers in patients with atrial fibrillation according to renal function.

BACKGROUND: Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. HYPOTHESIS: The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR). METHODS: The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. RESULTS: On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m2, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026). CONCLUSION: In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation.

Shenshuai Yingyang Jiaonang ameliorates chronic kidney disease-associated muscle atrophy in rats by inhibiting ferroptosis mediated by the HIF-1α/SLC7A11 pathway.

Objective: Shenshuai Yingyang Jiaonang (SSYYJN), a traditional Chinese medicine formula, can ameliorate muscle atrophy associated with chronic kidney disease (CKD). However, its mechanisms of action remain unclear. This study is to investigate the molecular mechanisms involved in the effects of SSYYJN in ameliorating muscle atrophy associated with CKD in rats. Methods: The chemical compounds of SSYYJN were identified by UPLC-Q-Orbitrap HRMS. Considering the dose-response relationship of the identified compounds, male SD rats were randomly divided into Sham, Model, SSYYJN, and α-Keto Acid (KA) groups. Subsequently, we assessed the therapeutic and anti-ferroptotic effects of SSYYJN. Network pharmacology studies were used to predict the molecular mechanism of SSYYJN on ferroptosis and were further verified for accuracy. Results: A total of 42 active compounds were identified from SSYYJN. SSYYJN alleviated muscle atrophy caused by CKD, as evidenced by changes in body weight, serum biochemical indices, mass and histopathology of the skeletal muscle, and the levels of MuRF1. SSYYJN reduced the levels of iron, MDA, and ROS, increased the levels of GSH, NAPDH, and Gpx4. Network pharmacology analysis indicated that SSYYJN exerted anti-ferroptotic effects that were closely related to the HIF-1α signaling pathway. Molecular protein and genetic test results showed that SSYYJN increased HIF-1α protein and increased SLC7A11. Conclusions: SSYYJN attenuates muscle atrophy in CKD by inhibiting ferroptosis through the activation of the HIF-1α/SLC7A11 pathway and might be a promising traditional Chinese medicine for muscle atrophy in CKD.

Shen Shuai II recipe improves renal hypoxia to attenuate renal injury in 5/6 renal ablation/infarction rats and effect evaluation using blood oxygenation level-dependent functional magnetic resonance imaging.

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD.

Reclassification of Genetic Testing Results: A Case Report Demonstrating the Need for Structured Re-Evaluation of Genetic Findings.

Rationale: Alport Syndrome (AS) is a progressive genetic condition characterized by chronic kidney disease (CKD), hearing loss, and eye abnormalities. It is caused by mutations in the genes COL4A3, COL4A4, and COL4A5. Heterozygous mutations in COL4A4 and COL4A3 cause autosomal dominant Alport Syndrome (ADAS), and a spectrum of phenotypes ranging from asymptomatic hematuria to CKD, with variable extra-renal features. In the past, heterozygous mutations in these genes were thought to be benign, however recent studies show that about 30% of patients can progress to CKD, and 15% can progress to end stage kidney disease (ESKD). Presenting Concerns: We present a case of a woman who was noted to have microscopic hematuria pre-living kidney donation. Genetic testing revealed a heterozygous variant of uncertain significance (VUS) in the COL4A4 gene. VUSs are medically nonactionable findings and data show that VUSs can be detected in 41% of all patients who undergo clinical genetic testing. VUSs frustrate clinicians and patients alike. Although they cannot be used in medical decision-making, data suggest that reanalysis can result in the reclassification of a VUS over time. Diagnosis: Post-donation, the index patient had a higher than anticipated rise in serum creatinine, raising a concern for possible intrinsic kidney disease. Kidney biopsy was deemed high risk in the setting of a unilateral kidney thereby limiting possible diagnostic intervention to determine the cause of disease. Intervention: Re-evaluation of prior genetic testing results and reassessment of the previously identified VUS in COL4A4 was performed 5-years post-donation. These analyses, along with the addition of new phenotypic data and extended pedigree data, resulted in the reclassification of the previously identified VUS to a likely pathogenic variant. Outcomes: This case demonstrates the importance of structured, periodic re-evaluation of genetic testing results. With the ever-changing landscape of genetics in medicine, the interpretation of a VUS can be dynamic and therefore warrant caution in living kidney donor evaluations. Studies have shown that about 10% of VUSs can be upgraded to a pathogenic classification after an 18- to 36-month interval. Structured re-evaluation of genomic testing results has not yet been integrated into clinical practice and poses a unique challenge in living kidney donation. Novel findings: This case report highlights the variability of the ADAS phenotype caused by pathogenic heterozygous variants in the type 4 collagen genes. It supports the nomenclature change from a benign hematuria phenotype to ADAS, particularly when additional risk factors such as proteinuria, focal segmental glomerulosclerosis or glomerular basement membrane changes on kidney biopsy are present, or as in this case, evidence of disease in other family members.

Justification: Le syndrome d'Alport (SA) est une maladie génétique progressive caractérisée par une insuffisance rénale chronique (IRC), une perte auditive et des anomalies oculaires. La maladie est causée par des mutations dans les gènes COL4A3, COL4A4 et COL4A5. Des mutations hétérozygotes dans les gènes COL4A4 et COL4A3 provoquent le syndrome d'Alport autosomique dominant (SAAD) et un specter de phénotypes allant de l'hématurie asymptomatique à l'IRC, avec des caractéristiques extrarénales variables. Dans le passé, les mutations hétérozygotes de ces gènes étaient considérées comme bénignes, mais des études récentes montrent qu'environ 30 % des patients peuvent progresser vers l'IRC et 15 % vers l'insuffisance rénale terminale (IRT). Présentation du cas: Nous présentons le cas d'une femme chez qui on avait observé une hématurie microscopique avant un don vivant de rein. Les tests génétiques ont révélé un variant hétérozygote de signification incertaine dans le gène COL4A4. Les variants de signification incertaine (VSI) sont des résultats qui ne peuvent être utilisés médicalement et les données montrent qu'ils peuvent être détectés chez 41 % des patients qui subissent des tests génétiques cliniques. Les VSI sont frustrants tant pour les cliniciens que pour les patients. Bien qu'ils ne puissent pas être utilisés dans la prise de décisions médicales, les données suggèrent que leur réanalyse pourrait entraîner leur reclassification au fil du temps. Diagnostic: Après le don, ce cas index a présenté une élévation de la créatinine sérique plus importante que prévu, ce qui a soulevé une préoccupation quant à la présence d'une néphropathie intrinsèque. La biopsie rénale a été jugée à haut risque dans le contexte de rein unilatéral, ce qui a limité la possible intervention diagnostique pour déterminer la cause de la maladie. Intervention: La réévaluation des résultats des tests génétiques antérieurs et du VSI précédemment identifié dans COL4A4 a été réalisée 5 ans après le don. Ces analyses, ainsi que l'ajout de nouvelles données phénotypiques et de données généalogiques étendues, ont abouti à la reclassification du VSI précédemment identifié en variant probablement pathogène. Résultats: Ce cas illustre l'importance de réévaluer de façon structurée et périodique les résultats des tests génétiques. La génétique étant en constante évolution en médecine, l'interprétation d'un VSI peut être dynamique et, ainsi, justifier la prudence dans les évaluations des donneurs de reins vivants. Des études ont montré qu'environ 10 % des VSI peuvent être reclassés comme pathogènes après 18 à 36 mois. La réévaluation structurée des résultats des tests génomiques, qui n'a pas encore été intégrée dans la pratique clinique, pose un défi unique dans le contexte d'un don vivant de reins. Principales observations: Ce rapport de cas met en évidence la variabilité du phénotype du SAAD causé par des variants hétérozygotes pathogènes dans les gènes du collagène de type 4. Il soutient un changement de nomenclature du phénotype d'hématurie bénigne en SAAD, en particulier en présence de facteurs de risque supplémentaires tels que la protéinurie et la glomérulosclérose segmentaire et focale, de modifications de la membrane basale glomérulaire sur la biopsie rénale ou, comme dans ce cas, de preuves de la maladie chez d'autres membres de la famille.

Predictors of chronic kidney disease survival in type 2 diabetes: a 12-year retrospective cohort study utilizing estimated glomerular filtration rate.

Predicting the course of kidney disease in individuals with both type 1 and type 2 diabetes mellitus (DM) is a significant clinical and policy challenge. In several regions, DM is now the leading cause of end-stage renal disease. The aim of this study to identify both modifiable and non-modifiable risk factors, along with clinical markers and coexisting conditions, that increase the likelihood of stage 3-5 chronic kidney disease (CKD) development in individuals with type 2 DM in the United Arab Emirates (UAE). This was a single-center retrospective cohort study based on data derived from electronic medical records of UAE patients with DM who were registered at outpatient clinics at Tawam Hospital in Al Ain, UAE, between January 2011 and December 2021. Type 2 DM patients aged ≥ 18 years who had serum HbA1c levels ≥ 6.5% were included in the study. Patients with type 1 DM, who had undergone permanent renal replacement therapy, who had under 1 year of follow-up, or who had missing or incomplete data were excluded from the study. Factors associated with diabetic patients developing stage 3-5 CKD were identified through Cox regression analysis and a fine and gray competing risk model to account for competing events that could potentially hinder the development of CKD. A total of 1003 patients were recruited for the study. The mean age of the study cohort at baseline was 70.6 ± 28.2 years. Several factors were found to increase the risk of developing stage 3-5 CKD: advancing age (HR 1.005, 95% CI 1.002-1.009, p = 0.026), a history of hypertension (HR 1.69, 95% CI 1.032-2.8, p = 0.037), a history of heart disease (HR 1.49, 95% CI 1.16-1.92, p = 0.002), elevated levels of serum creatinine (HR 1.006, 95% CI 1.002-1.010, p = 0.003), decreased levels of estimated glomerular filtration rate (eGFR) (HR 0.943, 95% CI, 0.938-0.947; p < 0.001), and the use of beta-blockers (HR 139, 95% CI 112-173, p = 0.003). Implementing preventative measures, initiating early interventions, and developing personalized care plans tailored to address specific risk factors are imperative for reducing the impact of CKD. Additionally, the unforeseen findings related to eGFR highlight the ongoing need for research to deepen our understanding of the complexities of kidney disease.

Diabetic kidney disease screening status and related factors: a cross-sectional study of patients with type 2 diabetes in six provinces in China.

OBJECTIVE: To understand the awareness and practice of diabetic kidney disease (DKD) or nephropathy screening among community-based patients with type 2 diabetes in six provinces and cities in China, and to analyse the related factors affecting screening practices. METHODS: From December 2021 to March 2022, a cross-sectional survey was conducted using a structured questionnaire in 6230 patients with type 2 diabetes aged 18 years and older. The content of the questionnaire includes three parts: the general situation of diabetic patients (gender, age, ethnicity, marriage, education, occupation, etc.), DKD screening practices, and the evaluation of DKD screening services. RESULTS: 89.70% of the patients had their fasting blood glucose measured every six months, 21.12% of the patients had their glycosylated hemoglobin measured every six months, and only 13.11% and 9.34% of the patients had a urine protein-creatinine ratio test and estimated glomerular filtration rate test every 12 months. The proportions of glycosylated hemoglobin, urine protein-creatinine ratio, and estimated glomerular filtration rate were relatively high in young, northern, highly educated, and long-duration type 2 diabetic patients. CONCLUSION: The results of this survey found that the proportion of urine protein-creatinine ratio testing, estimated glomerular filtration rate testing, and glycosylated hemoglobin testing in Chinese patients with type 2 diabetes was very low. Patients with type 2 diabetes in rural areas, southern areas, with low education level, and short course of disease have lower detection rates for DKD, and hence lower rates of prevention and treatment.

CFAP47 is a novel causative gene implicated in X-linked polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a well-described condition in which ~80% of cases have a genetic explanation, while the genetic basis of sporadic cystic kidney disease in adults remains unclear in ~30% of cases. This study aimed to identify novel genes associated with polycystic kidney disease (PKD) in patients with sporadic cystic kidney disease in which a clear genetic change was not identified in established genes. A next-generation sequencing panel analyzed known genes related to renal cysts in 118 sporadic cases, followed by whole-genome sequencing on 47 unrelated individuals without identified candidate variants. Three male patients were found to have rare missense variants in the X-linked gene Cilia And Flagella Associated Protein 47 (CFAP47). CFAP47 was expressed in primary cilia of human renal tubules, and knockout mice exhibited vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation. This discovery of CFAP47 as a newly identified gene associated with PKD, displaying X-linked inheritance, emphasizes the need for further cases to understand the role of CFAP47 in PKD.

A 20-year follow-up study of identical twin sisters with immunoglobulin A nephropathy.

Immunoglobulin A nephropathy (IgAN) is characterized by diverse clinicopathological phenotypes. Herein we present a follow-up study of previously reported identical twin sisters with IgAN. The older sister exhibited more severe kidney histopathology and proteinuria and a lower birthweight than did her younger sister, and only the older sister experienced two childbirths. These raised concerns regarding her kidney outcomes. However, with timely multidisciplinary treatments, the older sister's kidney function remained preserved after 20 years of IgAN history. Our findings indicate the significant contribution of environmental/epigenetic factors to IgAN progression and the need for tailored medical care corresponding to life events.

The Burden of Hypertension-Related Chronic Kidney Disease - China, 2010-2019.

What is already known about this topic?: The global burden of chronic kidney disease (CKD) is on the rise. What is added by this report?: In 2019, 5.58 million individuals in China were affected by CKD related to hypertension, leading to 70,260 fatalities and 1.69 million disability-adjusted life years (DALYs). The most affected groups were men, older individuals, and residents of western China. Over the period from 2010-2019, the age-standardized prevalence rate (ASPR) remained constant, and the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) showed a decreasing trend. However, there was an increase in the number of cases, deaths, and DALYs associated with this condition. What are the implications for public health practice?: Hypertension significantly contributes to the burden of CKD; therefore, raising awareness and implementing early screening measures are essential.

Determination of drug-related problems according to PAIR criteria in dialysis patients: a cross-sectional study in tertiary care hospital.

BACKGROUND: Dialysis patients are at high risk for drug-related problems (DRPs), which have significant consequences for their morbidity, mortality, and quality of life. Improved clinical outcomes can be achieved by preventing, identifying, and resolving these problems. METHODS: This is a retrospective observational study. In this study, the PAIR instrument (Pharmacotherapy Assessment in Chronic Renal Disease) was validated for use in Turkish. Validation consisted of three stages: translation back-translation with expert panel evaluation, reliability analysis using the test-retest method, and conceptual validity with both Pharmaceutical Care Network Europe (PCNE) and PAIR used to determine DRPs prevalence. RESULTS: In total, 104 patients (mean ± SD age, 54.1 ± 15.8 years; 53.8% male) were included in the study. An expert panel evaluated the items in the criterion based on their intelligibility, service of purpose, differentiation, and cultural suitability during the translation stage. Content validity index (CVI) score was found to be 0.95. The reliability analysis was performed by applying the test-retest method and calculating correlation coefficient on 30 randomly selected patients one month later. Correlation coefficient (p) was found to be 0.8. To evaluate conceptual validity, 104 patients' pharmacotherapy plans were assessed using both the PAIR and PCNE criteria. The prevalence of DRPs according to PAIR criteria (100.0%) and PCNE (73.1%) were statistically significantly different (p < 0.001). CONCLUSIONS: As a result, PAIR criteria can identify clinically relevant DRPs in patients with CKD and is a new, validated tool to be used in Turkey, but may not be adequate for patients receiving dialysis. Therefore, it needs to be reviewed and updated for dialysis patients.

Genetic or pharmacologic blockade of mPGES-2 attenuates renal lipotoxicity and diabetic kidney disease by targeting Rev-Erbα/FABP5 signaling.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and no specific drugs are clinically available. We have previously demonstrated that inhibiting microsomal prostaglandin E synthase-2 (mPGES-2) alleviated type 2 diabetes by enhancing ß cell function and promoting insulin production. However, the involvement of mPGES-2 in DKD remains unclear. Here, we aimed to analyze the association of enhanced mPGES-2 expression with impaired metabolic homeostasis of renal lipids and subsequent renal damage. Notably, global knockout or pharmacological blockage of mPGES-2 attenuated diabetic podocyte injury and tubulointerstitial fibrosis, thereby ameliorating lipid accumulation and lipotoxicity. These findings were further confirmed in podocyte- or tubule-specific mPGES-2-deficient mice. Mechanistically, mPGES-2 and Rev-Erbα competed for heme binding to regulate fatty acid binding protein 5 expression and lipid metabolism in the diabetic kidney. Our findings suggest a potential strategy for treating DKD via mPGES-2 inhibition.