The hepatocyte growth factor mimetic, ANG-3777, in kidney transplant recipients with delayed graft function: Results from a randomized phase 3 trial.

In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m2 at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.

Early Initiation of Sacubitril/Valsartan in Patients With Acute Heart Failure and Renal Dysfunction: An Analysis of the TRANSITION Study.

BACKGROUND: Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging owing to the risk of further deterioration in renal function, especially after acute decompensated HF (ADHF). METHODS AND RESULTS: We assessed the effect of RD (estimated glomerular filtration rate of ≥30 to <60 mL/min/1.73 m2) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized patients with HFrEF admitted for ADHF (RD, n = 476; non-RD, n = 483). At week 10, the target dose of sacubitril/valsartan (97/103 mg twice daily) was achieved by 42% patients in RD subgroup vs 54% in non-RD patients (P < .001). Sacubitril/valsartan was associated with greater estimated glomerular filtration rate improvements in RD subgroup than non-RD (change from baseline least squares mean 4.1 mL/min/1.73 m2, 95% confidence interval 2.2-6.1, P < .001). Cardiac biomarkers improved significantly in both subgroups; however, compared with the RD subgroup, the improvement was greater in those without RD (N-terminal pro-brain natriuretic peptide, -28.6% vs -44.8%, high-sensitivity troponin T -20.3% vs -33.9%) (P < .001). Patients in the RD subgroup compared with those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%, P < .001), investigator-reported cardiac failure (9.7% vs 5.6%, P = .029), and renal impairment (6.4% vs 2.1%, P = .002). CONCLUSIONS: Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated glomerular filtration rate and cardiac biomarkers. CLINICAL TRIAL REGISTRATION: NCT02661217.

Efficacy of denosumab in the treatment of hypercalcemic renal dysfunction in sarcoidosis: a case report.

A 70-year-old female patient was admitted for close examination and treatment of hypercalcemia (corrected serum calcium levels: 3.04 mmol/L) and renal dysfunction (serum creatinine levels: 254.59 µmol/L). The patient had a history of sarcoidosis, diagnosed based on epithelioid cell granulomas in subcutaneous nodule biopsies, uveitis, and bilateral hilar lymphadenopathy, which had spontaneously remitted 10 years before admission. Because the patient was diagnosed with hypercalcemia associated with recurrent sarcoidosis, prednisone (20 mg/day) was initiated, and its dose was tapered following the decrease in serum calcium and creatinine levels. However, the levels of these parameters increased again when the prednisone dose was reduced to ≤ 4 mg/day. We were concerned about glucocorticoid-induced osteoporosis in the patient but hesitated to use first-line bisphosphonates because of renal dysfunction. Therefore, denosumab was initiated to reduce the risk of hypercalcemia, renal dysfunction, and glucocorticoid-induced osteoporosis. Serum creatinine and corrected serum calcium levels subsequently decreased. The prednisone dose could be reduced following repeated denosumab administration.Thus, denosumab can be a multifaceted, beneficial option for sarcoidosis-induced hypercalcemia, as it alleviates renal dysfunction indirectly by normalizing serum calcium levels, facilitates reduction of the glucocorticoid dose, and ameliorates glucocorticoid-induced osteoporosis.

Triglyceride-Glucose Index Associated with Future Renal Function Decline in the General Population.

BACKGROUND: The triglyceride-glucose index (TyG index), calculated as the logarithmic product of fasting triglyceride and glucose concentrations, is recognized as a simple marker of insulin resistance. However, the association between the TyG index and future decline of renal function remains unclear in the general population. OBJECTIVE: To investigate whether the TyG index was associated with future decline of renal function in the general population who had not progressed to chronic kidney disease stage G2. DESIGN: Retrospective longitudinal observational cohort study. PARTICIPANTS: Individuals who received a population-based health checkup at JA Ehime Kouseiren Checkup Center from 2010 to 2019 (n = 134,007). Individuals without data of baseline fasting triglyceride or glucose levels, or baseline and follow-up data of estimated glomerular filtration rate (eGFR), or those with baseline eGFR < 60 mL/min/1.73 m2 were excluded. MAIN MEASURES: Future renal function decline, defined as a ≥ 25% decrease in eGFR from baseline. KEY RESULTS: Of 10,758 participants, 8,076 were classified into the low TyG index group (TyG index < 8.76, 1st to 3rd quartiles) and 2,682 into the high TyG index group (TyG index ≥ 8.76, 4th quartile). The mean follow-up period was 37.8 ± 23.6 months. The incidence rates of renal function decline were 0.31 and 0.69 per 100 person-years in the low and high TyG index groups, respectively. In multivariate Cox proportional hazard models, high TyG index was significantly associated with future renal function decline (hazard ratio 2.25, 95% CI 1.40-3.60). This association was consistent across subgroups stratified by age, sex, body mass index, baseline eGFR, and diagnosed hypertension, diabetes, or dyslipidemia. CONCLUSION: In the general population, high TyG index was associated with future renal function decline. The TyG index may be useful in identifying individuals at high risk for future renal function decline in the setting of health checkups.

Long-term albumin improves the outcomes of patients with decompensated cirrhosis and diabetes mellitus: Post hoc analysis of the ANSWER trial.

Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.

Renal Dysfunction at Discharge and Long-Term Survival in Acute Type A Aortic Dissection.

INTRODUCTION: We aimed to investigate the association between renal dysfunction at discharge and long-term survival in acute type A aortic dissection (ATAAD) patients following surgery. METHODS: From 2000 to 2021, 784 patients underwent aortic repair for an ATAAD. Patients were stratified based on creatinine (Cr) level at discharge alive or dead: normal Cr (n = 582) and elevated Cr defined as >1.3 mg/dL for males and >1.0 mg/dL for females or on dialysis at discharge (n = 202). RESULTS: Preoperatively, both groups had similar rates of comorbidities except for the elevated-Cr group which had more diabetes, chronic obstructive pulmonary disease, and chronic and acute renal insufficiency. Both groups had similar open ATAAD repair procedures. Postoperative outcomes in the elevated-Cr group were significantly worse, including six times higher operative mortality (20% versus 3.4%, P < 0.0001). The landmark long-term survival after discharge alive was significantly worse in the elevated-Cr group than the normal-Cr group (10-y survival: 48% versus 69%, P = 0.0009). The elevated Cr on dialysis at discharge group had significantly worse five-year survival (40%) than the elevated Cr not on dialysis at discharge group (80%, P = 0.02) and the normal-Cr group (87%, P < 0.0001). Additionally, the elevated Cr not on dialysis had a worse five-year survival than the normal-Cr group (80% versus 87%, P = 0.02). Elevated Cr at discharge on dialysis was a significant risk factor for late mortality (hazard ratio = 4.22, 95% confidence interval: [2.07, 8.61], P < 0.0001). CONCLUSIONS: Renal dysfunction at discharge was associated with significantly decreased short-term and long-term survival following open ATAAD repair. Surgeons should aggressively prevent renal dysfunction, especially new-onset dialysis, at discharge as it is correlated with significantly worse short-term and long-term outcomes.

Impairment of Cognitive Function Increases Mortality Risk in Relation to Cardiac Sympathetic Denervation and Renal Dysfunction in Patients With Systolic Heart Failure.

BACKGROUND: In contrast to the well-known prognostic values of the cardiorenal linkage, it remains unclear whether impaired cognitive function affects cardiac prognosis in relation to cardiac sympathetic innervation and renal function in patients with heart failure (HF).Methods and Results: A total of 433 consecutive HF patients with left ventricular ejection fraction (LVEF) <50% underwent the Mini-Mental State Examination (MMSE) and a neuropsychological test for screening of cognition impairment or subclinical dementia. Following metaiodobenzylguanidine (MIBG) scintigraphy, patient outcomes with a primary endpoint of lethal cardiac events (CEs) were evaluated for a mean period of 14.8 months. CEs were documented in 84 HF patients during follow-up. MMSE score, estimated glomerular filtration rate (eGFR) and standardized heart-to-mediastinum ratio of MIBG activity (sHMR) were significantly reduced in patients with CEs compared with patients without CEs. Furthermore, overall multivariate analysis revealed that these parameters were significant independent determinants of CEs. The cutoff values of MMSE score (<26), sHMR (<1.80) and eGFR (<47.0 mL/min/1.73 m2) determined by receiver operating characteristic (ROC) analysis successfully differentiated HF patients at more increased risk for CEs from other HF patients. CONCLUSIONS: Impairment of cognitive function is not only independently related to but also synergistically increases cardiac mortality risk in association with cardiac sympathetic function and renal function in patients with HF.

Association between Impaired Renal Function and Subclinical Myocardial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction: Assessment Using Noninvasive Pressure-Strain Loop.

INTRODUCTION: The objective of this study was to evaluate the abnormal myocardial function in HFpEF patients with renal dysfunction (RD) and investigate the relationship between renal function and myocardial mechanical characteristics in patients with HFpEF. METHODS: 134 patients with HFpEF and 32 control subjects were enrolled in our study. Clinical and echocardiography data were collected for offline analysis. Global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE) were measured after noninvasive pressure-strain loop analysis. Univariate and multivariate analyses were used to determine the correlation between renal function and myocardial function in patients with HFpEF. RESULTS: In comparison to control subjects, patients with HFpEF tend to have higher GWW (78 [50-115] vs. 108 [65-160] mm Hg%, p < 0.05) and lower GWE (96 [95-97] vs. 95 [92-96] %, p < 0.05), while left ventricular ejection fraction (65.5 ± 3.3 vs. 64.3 ± 4.6%, p < 0.05) was comparable between them. Besides, increased GWW (86 [58-152] vs. 125 [94-187] mm Hg%, p < 0.05) and decreased GWE (96 [93-97] vs. 94 [92-96] %, p < 0.05) were detected in patients with RD compared to those with normal renal function. An independent correlation was found between estimated glomerular filtration rate and GWW after multivariate analysis. DISCUSSION/CONCLUSION: More severely impaired myocardial function was detected in HFpEF patients with RD compared to those with normal renal function. Estimated glomerular filtration rate was independently correlated to GWW in patients with HFpEF.

Ophthalmic artery Doppler in women with hypertensive disorders of pregnancy: relationship to blood pressure control and renal dysfunction at 6-9 weeks postnatally.

OBJECTIVES: To examine the postnatal course of ophthalmic artery (OA) Doppler in women with hypertensive disorders of pregnancy (HDP) and to evaluate the correlation between OA Doppler parameters and poor postnatal blood pressure control and renal dysfunction at 2-3 weeks and 6-9 weeks postnatally. METHODS: This was a prospective cohort study of women with a singleton pregnancy and HDP seen at a tertiary pregnancy hypertension clinic between 2019 and 2021. Three visits were included: Visit 1, the last visit to the antenatal hypertension clinic within 2 weeks prior to delivery; Visit 2, at 2-3 weeks postnatally; and Visit 3, at 6-9 weeks postnatally. At each visit, maternal demographic characteristics, medical history, blood pressure and OA Doppler were obtained. In addition, fetal growth and fetal Dopplers were examined antenatally and, at 6-9 weeks postnatally, estimated glomerular filtration rate and proteinuria were quantified. Study participants were divided into four hypertension groups, according to longitudinal changes in blood pressure at the three visits. For the postnatal visits, hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg in the absence of antihypertensive medication, and SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg whilst taking antihypertensives. Group 1 was hypertensive at all three visits; Group 2 was hypertensive at Visits 1 and 2 but normotensive at Visit 3; Group 3 was hypertensive at Visits 1 and 3 but normotensive at Visit 2; and Group 4 was hypertensive at Visit 1 but normotensive at Visits 2 and 3. The longitudinal changes in mean arterial pressure (MAP), peak systolic velocity (PSV) 1, PSV2 and the ratio of PSV2/PSV1 over the three timepoints were examined by a repeated-measures, multilevel, linear mixed-effects analysis, controlling for maternal age, weight at presentation and use of antihypertensive medication. In addition, we examined the longitudinal change in OA Doppler parameters in women with different degrees of postnatal blood pressure control and in those with and those without renal dysfunction at 6-9 weeks postnatally. RESULTS: A total of 108 women were recruited to the study, of whom 86 had new-onset hypertension and 22 had chronic hypertension. When controlling for maternal age, weight at presentation and use of antihypertensive medication, a significant decline in log10 MAP (P < 0.001), log10 PSV1 (P < 0.001) and log10 PSV2 (P = 0.01) was seen between Visits 1 and 3. Log10 PSVR did not change with time. When assessing OA Doppler against hypertension group, log10 PSV1 and log10 PSV2 did not differ between the hypertension groups, whilst Group 4 had a lower log10 PSVR compared with Group 1 (P < 0.01), Group 2 (P = 0.03) and Group 3 (P < 0.01). At 6-9 weeks postnatally, log10 PSVR was lower in those without compared to those with renal dysfunction (-0.021, P = 0.01), whilst log10 MAP, log10 PSV1 and log10 PSV2 values did not differ. Log10 PSVR did not change with time and remained at -0.12 (95% CI, -0.13 to -0.11) across the three visits. CONCLUSIONS: In women with HDP, the OA-PSVR was significantly higher in those with labile or persistently raised blood pressure postnatally compared to women whose blood pressure normalized. Similarly, the OA-PSVR at 6-9 weeks postnatally was significantly higher in women with renal dysfunction vs those without dysfunction. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Association of the predicted free blood concentration of teicoplanin with the development of renal dysfunction.

PURPOSE: In clinical practice, teicoplanin (TEIC) is typically administered at a trough concentration of 15-40 µg/mL. TEIC has a protein binding rate of approximately 90%, and its concentration rarely exceeds 40 µg/ml. Nevertheless, an increase in the free blood trough concentration may result in renal dysfunction. However, the relationship between the free blood trough concentration and the occurrence of renal dysfunction remains unclear. This study aimed to examine the impact of the predicted free blood concentration on the development of renal dysfunction. METHODS: This retrospective study included patients who underwent TEIC and had at least one trough concentration measurement. The association between the frequency of renal dysfunction occurrence and the predicted free blood concentration was evaluated using the following equation: free TEIC concentration = total TEIC concentration/(1 + 1.78 × serum albumin level). RESULTS: Of the 170 patients included in this study, 18% (31/170) developed renal dysfunction. The predicted free trough concentration was significantly higher in the renal dysfunction onset group than in the nononset group. However, the total trough concentration was not significantly associated with the development of renal dysfunction. The odds ratio for developing renal dysfunction was 4.5 (95% confidence interval, 1.9-10.5; P < 0.001) when the predicted free trough concentration was > 4.0 µg/mL. CONCLUSION: Elevated free trough concentrations of TEIC were associated with an increased risk of renal dysfunction. Controlling the increase in the predicted free blood concentration may effectively prevent the development of renal dysfunction.

Poor performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal dysfunction.

PURPOSE: Clinical decision support systems (CDSS) are used to identify drugs with potential need for dose modification in patients with renal impairment. ChatGPT holds the potential to be integrated in the electronic health record (EHR) system to give such dosing advices. In this study, we aim to evaluate the performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal impairment. METHODS: This cross-sectional study was performed at Tergooi Medical Center, the Netherlands. CDSS alerts regarding renal dysfunction were collected from the electronic health record (EHR) during a 2-week period and were presented to ChatGPT and an expert panel. Alerts were presented with and without patient variables. To evaluate the performance, suggested medication interventions were compared. RESULTS: In total, 172 CDDS alerts were generated for 80 patients. Indecisive responses by ChatGPT to alerts were excluded. For alerts presented without patient variables, ChatGPT provided "correct and identical" responses to 19.9%, "correct and different" responses to 26.7%, and "incorrect responses to 53.4% of the alerts. For alerts including patient variables, ChatGPT provided "correct and identical" responses to 16.7%, "correct and different" responses to 16.0%, and "incorrect responses to 67.3% of the alerts. Accuracy was better for newer drugs such as direct oral anticoagulants. CONCLUSION: The performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal dysfunction was poor. Based on these results, we conclude that ChatGPT, in its current state, is not appropriate for automatic integration into our EHR to handle CDSS alerts related to renal dysfunction.

Clinical features, future cardiac events, and prognostic factors following percutaneous coronary intervention in young female patients.

BACKGROUND: The proportion of young females among the patients who undergo percutaneous coronary intervention (PCI) is relatively small, and information on their clinical characteristics is limited. This study investigated the clinical characteristics and prognostic factors for future cardiac events in young females who underwent PCI. METHODS: This multicenter observational study included 187 consecutive female patients aged < 60 years who underwent PCI in seven hospitals. The primary composite endpoint was the incidence of cardiac death, nonfatal myocardial infarction, and target vessel revascularization. RESULTS: The mean patient age was 52.1 ± 6.1 years and 89 (47.6%) had diabetes, and renal dysfunction (an estimated glomerular filtration rate < 60 mL/min/1.73 m2) was observed in 38 (20.3%). During a median follow-up of 3.3 years, the primary endpoint occurred in 28 patients. The Cox proportional hazards models showed that renal dysfunction was an independent predictor for the primary endpoint (hazard ratio 3.04, 95% confidence interval 1.25-7.40, p = 0.01), as well as multivessel disease (hazard ratio 2.79, 95% confidence interval 1.12-6.93, p = 0.03). Patients with renal dysfunction had a significantly higher risk for the primary endpoint than those without renal dysfunction. CONCLUSIONS: Renal dysfunction was strongly associated with future cardiac events in young females who underwent PCI.

Three cases of hospitalized Legionella pneumonia patients successfully treated with lascufloxacin.

Legionella pneumonia is one of the major causes of severe pneumonia, in which treatment delay might lead to a poor prognosis. Therefore, as far as possible, early diagnosis and treatment of Legionella pneumonia is essential. Regarding the antimicrobials for Legionella pneumonia, fluoroquinolones, such as levofloxacin, or macrolides, such as azithromycin (AZM), are recommended in Japan and other countries. Lascufloxacin (LSFX), the newest fluoroquinolone developed in Japan, has been in use in daily clinical practice since January 2020. However, there are only few reports of Legionella pneumonia cases treated with LSFX. Here, we report three cases of hospitalized Legionella pneumonia patients that were successfully treated using LSFX. All three patients were admitted to the medical ward on admission, although one patient was subsequently transferred to the ICU for mechanical ventilatory management due to worsening of the pneumonia on day 3. All patients improved and were discharged following LSFX treatment (the patient admitted to the ICU was treated using LSFX + AZM combination therapy) without any severe adverse events. LSFX might be considered to be the first antibiotic choice for Legionella pneumonia, similar to levofloxacin. However, further data regarding the treatment of Legionella pneumonia cases using LSFX are needed to evaluate its efficacy and safety.

Association of Preoperative Renal-Resistive Index With Long-term Renal and Cardiovascular Outcomes After Cardiac Surgery.

OBJECTIVE: To investigate the association of elevated preoperative renal-resistive index (RRI) with persistent renal dysfunction, major adverse kidney events (MAKE), and major adverse cardiovascular events (MACE) after cardiac surgery. DESIGN: Observational cohort study. SETTING: University hospital. PARTICIPANTS: Ninety-six adult patients undergoing cardiac surgery. INTERVENTIONS: RRI measurement the day before surgery. MEASUREMENTS AND MAIN RESULTS: Fifty-eight patients (60%) had elevated RRI ≥0.70. Five years after surgery, persistent renal dysfunction (sustained decline in estimated glomerular filtration rate ≥25%) had occurred in 25 patients (26%), MAKE (persistent renal dysfunction, renal replacement therapy, or death) in 34 (35%), and MACE (myocardial infarction, unstable angina, decompensated heart failure, stroke, or cardiovascular death) in 28 (29%). RRI was higher in patients who developed persistent renal dysfunction (median, 0.78 [IQR, 0.74-0.82] v 0.70 [0.66-0.77], p = 0.001), MAKE (0.77 [0.72-0.81] v 0.68 [0.65-0.76], p = 0.002), and MACE (0.77 [0.72-0.81] v 0.70 [0.66-0.77], p = 0.006). Patients with elevated RRI had a significantly higher cumulative incidence of all long-term outcomes. After adjustment for baseline renal function and heart failure, elevated RRI was associated with persistent renal dysfunction (hazard ratio [HR], 5.82 [95% CI, 1.71-19.9]), MAKE (HR, 4.21 [1.59-11.1]), and MACE (HR, 2.81 [1.03-7.65]). CONCLUSIONS: Elevated preoperative RRI is associated with persistent renal dysfunction, MAKE, and MACE after cardiac surgery. Preoperative RRI may be used for long-term risk assessment in patients undergoing cardiac surgery.

Treatment with Rasburicase in Hospitalized Patients with Cardiorenal Syndrome: Old Treatment, New Scenario.

Cardiorenal syndrome (CRS) involves joint dysfunction of the heart and kidney. Acute forms share biochemical alterations like hyperuricaemia (HU) with tumour lysis syndrome (TLS). The mainstay treatment of acute CRS with systemic overload is diuretics, but rasburicase is used in TLS to prevent and treat hyperuricaemia. An observational, retrospective study was performed to assess the effectiveness and safety of a single dose of rasburicase in hospitalized patients with cardiorenal syndrome, worsening renal function and uric acid levels above 9 mg/dL. Rasburicase improved diuresis and systemic congestion in the 35 patients included. A total of 86% of patients did not need to undergo RRT, and early withdrawal was possible in the remaining five. Creatinine (Cr) decreased after treatment with rasburicase from a peak of 3.6 ± 1.27 to 1.79 ± 0.83 mg/dL, and the estimated glomerular filtration rate (eGFR) improved from 17 ± 8 to 41 ± 20 mL/min/1.73 m2 (p = 0.0001). The levels of N-terminal type B Brain Natriuretic Peptide (Nt-ProBNP) and C-reactive protein (CRP) were also significantly reduced. No relevant adverse events were detected. Our results show that early treatment with a dose of rasburicase in patients with CRS and severe HU is effective to improve renal function and systemic congestion, avoiding the need for sustained extrarenal clearance, regardless of comorbidities and ventricular function.

Nephrolithiasis and/or nephrocalcinosis is significantly related to renal dysfunction in patients with primary Sjögren's syndrome.

OBJECTIVE: The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. METHODS: The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody-positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. RESULTS: Of the 68 patients with anti-SSA-antibody-positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary ß2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. CONCLUSION: Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS.

A Comparative Study on the Efficacy Between Cystatin C and Creatinine-Based Equations for Early Detection of Renal Damage in Patients of Eastern India.

Chronic kidney disease (CKD) is one of the leading causes of mortality across the globe. Early diagnosis of the disease is important in order to prevent the adverse outcome related to CKD. Many laboratories adopt creatinine-based e-GFR equations which yields imprecise results leading to misdiagnosis of CKD. Emerging studies indicated cystatin C as a better renal marker than creatinine. The aim of the study is to compare the efficacy of CKD epidemiology collaboration (CKD-EPI) creatinine e-GFR equations with (CKD EPI) cystatin-based e-GFR equations alone and in combination with creatinine for early detection of CKD. A cross-sectional study employing 473 patients was conducted. Three estimating GFR equations were calculated based on creatinine and cystatin C. Pearson Correlation study was done to assess the correlation of creatinine and cystatin C with their respective GFRs. A predictive model was developed, and ROC curve was constructed to compare efficacy, sensitivity and specificity of the creatinine and cystatin C based equations. Cystatin C exhibited better negative correlation with GFR than creatinine in correlation study performed with three commonly employed eGFR equations including  CKD EPI Creatine cystatin C combined  equation (2021), cys C alone and CKD EPI  creatinine (2021)  equations respectively[r=(-) 0.801 vs. r=(-)0.786 vs. r=(-)0.773]. Predictive model demonstrated highest efficiency, sensitivity and specificity for creatinine-cystatin C combined equation (88%, 81% and 93%) followed by cystatin C alone equation (73%,63% and 82%) and creatinine-based equation  (61%, 56% and 66% respectively). The study showed better performance of cystatin C based equations for early detection of advance stages in chronic kidney disease as compared to creatinine-based e-GFR equation.

Up-regulation of PRKDC was associated with poor renal dysfunction after renal transplantation: A multi-centre analysis.

Renal transplantation is the only efficacious treatment for end-stage kidney disease. However, some people have developed renal insufficiency after transplantation, the mechanisms of which have not been well clarified. Previous studies have focused on patient factors, while the effect of gene expression in the donor kidney on post-transplant renal function has been less studied. Donor kidney clinical data and mRNA expression status were extracted from the GEO database (GSE147451). Weight gene co-expression network analysis (WGCNA) and differential gene enrichment analysis were performed. For external validation, we collected data from 122 patients who accepted renal transplantation at several hospitals and measured the level of target genes by qPCR. This study included 192 patients from the GEO data set, and 13 co-expressed genes were confirmed by WGCNA and differential gene enrichment analysis. Then, the PPI network contained 17 edges as well as 12 nodes, and four central genes (PRKDC, RFC5, RFC3 and RBM14) were identified. We found by collecting data from 122 patients who underwent renal transplantation in several hospitals and by multivariate logistic regression that acute graft-versus-host disease postoperative infection, PRKDC [Hazard Ratio (HR) = 4.44; 95% CI = [1.60, 13.68]; p = 0.006] mRNA level correlated with the renal function after transplantation. The prediction model constructed had good predictive accuracy (C-index = 0.886). Elevated levels of donor kidney PRKDC are associated with renal dysfunction after transplantation. The prediction model of renal function status for post-transplant recipients based on PRKDC has good predictive accuracy and clinical application.

Effect of renal function under left ventricular assist device support on the cardiac function and clinical events after heart transplantation.

AIM: We investigated the effects of pre-transplantation renal dysfunction under left ventricular assisted device (LVAD) support on post-transplantation cardiac function, and patient prognosis after heart transplantation (HTx). METHOD: All patients who were bridged by LVAD and underwent HTx at our hospital between 2007 and 2022 were included in this study. Patients were classified into two groups based on estimated glomerular filtration rate (eGFR) before HTx: renal dysfunction (RD) group (eGFR < 60 mL/min/1.73 m2 ) and non-renal dysfunction (NRD) group. RESULT: A total of 132 patients were analyzed, of whom 48 were classified into the RD group and 84 into the NRD group (RD group, 47.9 ± 10.1 years; NRD group, 38.4 ± 11.9 years, p < .0001). Under LVAD support before HTx, the RD group tended to have a history of right ventricular failure (RD group, nine (19%); NRD group, seven (8%); p = .098). After HTx, the echocardiographic parameters did not differ between the two groups in the long term. Furthermore, more concise hemodynamic parameters, exemplified by right heart catheterization, were not significantly different between the two groups. Regarding graft rejection, no significant differences were found in acute cellular rejection and cardiac allograft vasculopathy following HTx. In contrast, patients with RD before HTx had significantly increased mortality in the chronic phase after HTx and initiation of maintenance dialysis, without any overt changes in cardiac function. CONCLUSION: Pre-transplantation renal dysfunction under LVAD support significantly affected clinical course after HTx without any overt changes in graft cardiac function.

Gaining consensus around patient risk groups and prognostic profiles to guide CMV management among patients with solid organ transplant: Insights from a Delphi panel with SOT experts.

INTRODUCTION: This study aimed to characterize patient risk groups and respective prognostic profiles to optimize clinical decision-making and guide appropriate medical cytomegalovirus (CMV) management among patients with solid organ transplant (SOT). METHODS: Between September 2021 and February 2022, a three-round modified Delphi study was conducted to generate consensus among 14 international experts in virology and organ transplantation. Experts were asked about treatment and prognoses for patients in seven distinct clinical scenarios. Furthermore, experts were asked to risk-stratify patients by pre-/post-transplant characteristics. Consensus around opting for/against a treatment was observed if ≥75% or <25% of experts reported ≥50% likelihood to recommend or if treatments were ranked inside/outside the top two options and ≥75% of experts were within 1 standard deviation of the mean rank. RESULTS: Experts agreed on several unmet needs in CMV disease management post-SOT, particularly avoidance of treatment-limiting toxicities with conventional CMV therapy and emergence of both primary refractory and drug resistant treatment failures. Experts considered CMV viral load, resistance profile, and route of administration as critical to treatment selection. For newer CMV therapeutic options, experts listed lack of long-term use data, concerns over potential resistance, high cost and limited availability as challenges restricting adoption, and successful patient management. CONCLUSION: Experts achieved consensus around patient risk stratifications and factors influencing therapeutic options. Recommendations emerging from this Delphi study may support practicing physicians when confronted with challenging CMV scenarios in SOT patients, but additional experiences with newer anti-CMV agents are needed to re-validate expert consensus and update post-transplant CMV guidelines.