Risk Of Kidney Failure Research Articles

Impact of Overweight on Renal Prognosis in Malignant Hypertension Patients With Thrombotic Microangiopathy.

Overweight and obesity is a risk factor for hypertension. Malignant hypertension (MHT) is the most severe form of hypertension, and thrombotic microangiopathy (TMA), one of its complications, has been linked to significant renal outcomes. However, the impact of overweight and obesity on renal prognosis in MHT patients with TMA is not well understood. This was a prospective cohort enrolled 288 MHT patients with renal TMA from 2008 to 2023. The clinical and histopathological characteristics were recorded based on body mass index (BMI, < 25 and ≥ 25 kg/m2). The outcome was the incidence of kidney failure. The associations of BMI with kidney failure were examined in logistic regression models. Among 288 patients, 180 (62.5%) progressed to kidney failure, including 113 (68.5%) patients with BMI < 25 kg/m2. Participants with obesity had higher levels of hemoglobin, estimated glomerular filtration rate and C3, but lower levels of serum creatinine and IgA nephropathy. BMI ≥ 25 kg/m2 was associated with a better outcome of kidney failure in MHT patients with TMA (odd ratios [ORs]: 0.49 [95% confidence interval (CI): 0.27-0.91], p = 0.025). Male, uric acid, onion skin lesions, and global sclerosis ratio were correlated with higher risk of kidney failure; serum albumin and treatment with renin-angiotensin system blockers were related to lower risk of kidney failure. In MHT patients with renal TMA, normal-weight rather than overweight was found to associate with a worse renal prognosis. Management efforts for MHT may be directed toward controlling body weight within a reasonable range for patients.

Prediction of Allograft Failure in Pediatric Kidney Transplant Recipients: A Validation Study of the Four-Variable Kidney Failure Risk Equation

Prediction of Allograft Failure in Pediatric Kidney Transplant Recipients: A Validation Study of the Four-Variable Kidney Failure Risk Equation

Lower Risk of Death and Kidney Failure Associated with Higher Target (vs. Below-Target) Doses of RAS Inhibitors in Octogenarians with HFrEF

Lower Risk of Death and Kidney Failure Associated with Higher Target (vs. Below-Target) Doses of RAS Inhibitors in Octogenarians with HFrEF

Automated digital counselling promotes therapeutic change in mental health in patients with chronic heart failure or chronic kidney disease: ODYSSEE-vCHAT study

Abstract Background The efficacy of digital programs to improve the management of chronic heart failure (CHF) and chronic kidney disease (CKD) is not established. Building on related studies in digital health, behavioural counselling, and social support, we evaluated whether an automated digital counselling program with social network support (ODYSSEE-vCHAT) could improve mental health and health-related quality of life in patients with CHF or CKD. Purpose The primary objective was to examine whether engagement with ODYSSEE-vCHAT was associated with a minimal clinically important difference for improvement in the Mental Component Summary (MCS) of the SF-36 at end-of-study. Secondary outcomes included: ENRICHD Social Support Index (ESSI), Patient Health Questionnaire for Depression (PHQ-9) Godin-Shephard Leisure Time Physical Activity Scale (GSLTPAQ), and an index of the frequency to which patients engaged in goal-directed activities for living well (EUROIA). Methods ODYSSEE-vCHAT was a multi-centre, single group, open label study with assessments at baseline and end-of-study (approximately 11 months). Inclusion criteria were: ≥18 years of age, diagnosis of CHF (reduced ejection fraction (EF) ≤ 40%, mid-range EF, 41-49%, or preserved EF ≥ 50%); or CKD diagnosis (&amp;gt;10% risk for dialysis using the 4-variable, 2-year Kidney Failure Risk Equation, or on dialysis). Exclusion was based on inability to participate due to co-morbidities. The digital counselling protocol taught self-care skills to improve mental health, quality of life, and adherence to medications, exercise, diet, and smoke-free living (Figure 1). Patient engagement with ODYSSEE-vCHAT was defined as Not Engaged (0 logon minutes) vs. Engaged (&amp;gt; 0 logon minutes). The primary outcome was a minimal clinically important difference for MCS change: ΔMCS ≥ 3.8 or MCS ≥ 65 at baseline and study endpoint. It was assessed using multivariable binary logistic regression, controlling for exposure to COVID-19 and health literacy. Secondary outcomes were assessed using multivariable linear regression analyses with the same covariates. Results 215 patients were enrolled. There were 7 deaths and 34 withdrew. In our sample of 174 patients, mean age = 54.4 years (95% Confidence Interval, CI, 25, 81), gender identity as women, n = 68 (39%), ethno-racial group other than White, n = 83, (48%), primary diagnosis, CHF, n = 68 (39%), and CKD, n = 106 (61%). Duration of enrolment to end-of-study: median = 352 days, (95% CI, 159, 496). Engagement with ODYSSEE was associated with therapeutic change on the MCS (for both CHF and CKD patients, and CHF patients alone), GSLTPAQ, and EUROIA, but not the PHQ9 or ESSI (Figure 2). Conclusions Automated digital counselling with social network support promotes improvement in indices of mental health for patients with CHF and CKD. These findings support a follow-up randomized controlled trial.Figure 1.ODYSSEE-vCHAT Study ProtocolFiFigure 2.ODYSSEE-vCHAT Study Outcomes

Kidney and cardiovascular outcomes in older population with mildly to moderately decreased kidney function - A nationwide cohort study.

Although the prevalence of chronic kidney disease (CKD) is increasing in the aging population, the clinical relevance of the CKD definition (glomerular filtration rate [GFR] &lt; 60 ml/min/1.73 m2) in older populations remains debatable. We investigated the clinical outcomes in older populations with mildly to moderately decreased GFR (45-59 ml/min/1.73 m2, CKD stage 3A). A total of 7,789,242 participants aged ≥ 40 years with estimated GFR (eGFR) ≥ 45 ml/min/1.73 m2 in national health screening examination from 2012 to 2017 were included in this retrospective cohort study using the Korean National Health Insurance Service database. The main outcomes included kidney failure, cardiovascular disease (CVD), and all-cause death. Cox regression hazard models were used to estimate the hazard ratios. The proportion of participants with eGFR 45-59 ml/min/1.73 m2 was 10.0% and 16.3% in the old (65-74 years) and very old (75 ≥ years) groups, respectively. Mildly to moderately decreased eGFR was associated with a higher risk of kidney failure, CVD, and all-cause death compared with eGFR 60-89 ml/min/1.73 m2 in the old and very old groups, regardless of proteinuria (adjusted hazard ratio [95% confidence interval] in the very old group without proteinuria: kidney failure 3.048 [2.495-3.722], CVD 1.103 [1.066-1.142], and all-cause death 1.172 [1.144-1.201]). Mildly to moderately decreased eGFR was associated with an increased risk of kidney failure, CVD, and all-cause death in the older population, regardless of proteinuria, suggesting the importance of appropriate monitoring and management in this population.

Atrasentan in Patients with IgA Nephropathy.

Patients with IgA nephropathy and severe proteinuria have a high lifetime risk of kidney failure. The efficacy and safety of the selective endothelin type A receptor antagonist atrasentan in reducing proteinuria in patients with IgA nephropathy are incompletely understood. We are conducting a phase 3, multinational, double-blind, randomized, controlled trial involving adults with biopsy-proven IgA nephropathy, a total urinary protein excretion of at least 1 g per day, and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. Patients were randomly assigned to receive atrasentan (0.75 mg per day) or matched placebo for 132 weeks. The primary outcome, assessed at a prespecified interim analysis of data from the first 270 patients in the main stratum, was the change in the 24-hour urinary protein-to-creatinine ratio from baseline to week 36; the change was estimated with the use of a repeated-measures model. (An exploratory stratum of patients who were receiving a sodium-glucose cotransporter 2 inhibitor were included in a separate analysis.) Safety analyses were based on adverse events across the entire main stratum. A total of 340 patients were recruited into the main stratum. Among the first 270 patients in the main stratum (135 per trial group) who completed the week 36 visit, the geometric mean percentage change in the urinary protein-to-creatinine ratio relative to baseline was significantly greater with atrasentan (-38.1%) than with placebo (-3.1%), with a geometric mean between-group difference of -36.1 percentage points (95% confidence interval, -44.6 to -26.4; P<0.001). The percentage of patients with adverse events did not differ substantially between the two groups. Fluid retention was reported by 19 of 169 patients (11.2%) in the atrasentan group and in 14 of 170 (8.2%) in the placebo group but did not lead to discontinuation of the trial regimen. No apparent cases of cardiac failure or severe edema occurred. In this prespecified interim analysis, atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo in patients with IgA nephropathy. (Funded by Novartis; ALIGN ClinicalTrials.gov number, NCT04573478.).

Adding Biomarker Change Information to the Kidney Failure Risk Equation Improves Predictive Ability for Dialysis Dependency in eGFR &amp;lt;30 mL/min/1.73m2

Abstract Background Although the Kidney Failure Risk Equation (KFRE), a well-known predictive model for predicting dialysis dependency, is useful, it remains unclear whether the addition of biomarker changes to the KFRE model in patients with an estimated glomerular filtration rate (eGFR) &amp;lt; 30 mL/min/1.73 m2 will improve its predictive value. Methods We retrospectively identified adults with eGFR &amp;lt; 30 mL/min/1.73 m2 without dialysis dependency, and available health checkup data for 2 successive years using a large Japanese claims database (DeSC, Tokyo, Japan). We dichotomized the entire population into 50% training set and the other half as validation set. To assess the incremental value in the predictive ability for dialysis dependency by the addition of changes in eGFR and proteinuria, we calculated the difference in the C-statistics and net reclassification index (NRI). Results We identified 4,499 individuals and observed 422 individuals (incidence of 45.2 per 1000 person-years) who developed dialysis dependency during the observation period (9,343 person-years). Adding biomarker changes to the KFRE model improved C-statistics from 0.862 to 0.921, with an improvement of 0.060 (95% CI of 0.043–0.076, P &amp;lt;0.001). The corresponding NRI was 0.773 (95% CI: 0.637– 0.908), with an NRI for events of 0.544 (95% CI of 0.415–0.672) and NRI for non-events of 0.229 (95% CI of 0.186–0.272). Conclusions The KFRE model was improved by incorporating yearly changes in its components. The added information may help clinicians identify high-risk individuals and improve their care.

Development and validation of a chronic kidney disease progression model using patient-level simulations

Chronic disease progression models are available for several highly prevalent conditions. For chronic kidney disease (CKD), the scope of existing progression models is limited to the risk of kidney failure and major cardiovascular (CV) events. The aim of this project was to develop a comprehensive CKD progression model (CKD-PM) that simulates the risk of CKD progression and a broad range of complications in patients with CKD. A series of literature reviews informed the selection of risk factors and identified existing risk equations/algorithms for kidney replacement therapy (KRT), CV events, other CKD-related complications, and mortality. Risk equations and transition probabilities were primarily sourced from publications produced by large US and international CKD registries. A patient-level, state-transition model was developed with health states defined by the Kidney Disease Improving Global Outcomes categories. Model validation was performed by comparing predicted outcomes with observed outcomes in the source cohorts used in model development (internal validation) and other cohorts (external validation). The CKD-PM demonstrated satisfactory modeling properties. Accurate prediction of all-cause and CV mortality was achieved without calibration, while prediction of CV events through CKD-specific equations required implementation of a calibration factor to balance time-dependent versus baseline risk. Predicted annual changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio were acceptable in comparison to external values. A flexible eGFR threshold for KRT equations enabled accurate prediction of these events. This CKD-PM demonstrated reliable modeling properties. Both internal and external validation revealed robust outcomes.

Potential benefits of hormone replacement therapy on cardiovascular and kidney outcomes in postmenopausal women with chronic kidney disease.

Hormone replacement therapy (HRT) is recommended for alleviating vasomotor symptoms or preventing bone loss in postmenopausal women. This study aimed to investigate the impact of hormone replacement therapy on major adverse cardiovascular events, kidney failure, and mortality in women with chronic kidney disease (CKD). This population-based cohort study analyzed data from the National Cancer Screening Program and the national health examination of South Korea. Data on postmenopausal women were extracted from the 2009 National Cancer Screening Program. Among these postmenopausal women, those with CKD without kidney replacement therapy were selected through a national health examination from 2009 to 2013. The study outcomes were the risks of major adverse cardiovascular events, kidney failure, and all-cause mortality according to hormone replacement therapy. A total of 768,279 postmenopausal women with CKD were enrolled in this study; of these women, 13.8% (N = 106,052) had a history of hormone replacement therapy. The user and non-user groups differed with respect to baseline characteristics, with the latter being older and having risk factors for cardiovascular disease. After adjustment for confounding factors, the group exposed tohormone replacement therapyshowed lower risks of major adverse cardiovascular events, kidney failure, and all-cause mortality. This study suggests the potential benefits of hormone replacement therapy in postmenopausal women with CKD and highlighted its potential advantages for cardiovascular and kidney outcomes.

Perbedaan Perubahan Tekanan Darah Antara yang Diberikan Jus Mentimun (Cucumis Sativus Linn) dengan Jus Pepaya (Carica Papaya) Terhadap Penderita Hipertensi Primer di Wilayah Kerja Puskesmas Ampenan

Hypertension is the leading cause of death in Indonesia and has a high risk of heart failure, stroke, kidney failure and myocardial infarction. Management of hypertension includes lifestyle changes, diet, stress management and others. In addition, giving cucumber juice and papaya juice is also recommended as a nursing management to lower blood pressure because the content of potassium, magnesium, phosphorus can treat hypertension. The purpose of this study was to determine the difference in blood pressure changes between those given cucumber juice (cucumis sativus linn) and papaya juice (carica papaya) for patients with primary hypertension in the Ampenan Health Center work area. The research method used was a Quasy Experimental study with a pretest-posttest control group design with a quantitative approach in the cucumber juice group and the papaya juice group with a control group without treatment. Random sampling technique was used to obtain 30 respondents divided into 3 groups. The results of the study showed that the results of the dependent t test showed a p value = &lt;0.05 so that there was a difference in blood pressure reduction between those given cucumber juice and those given papaya juice in patients with hypertension.

Representation of multimorbidity and frailty in the development and validation of kidney failure prognostic prediction models: a systematic review

BackgroundPrognostic models that identify individuals with chronic kidney disease (CKD) at greatest risk of developing kidney failure help clinicians to make decisions and deliver precision medicine. It is recognised that people with CKD usually have multiple long-term health conditions (multimorbidity) and often experience frailty. We undertook a systematic review to evaluate the representation and consideration of multimorbidity and frailty within CKD cohorts used to develop and/or validate prognostic models assessing the risk of kidney failure.MethodsWe identified studies that described derivation, validation or update of kidney failure prognostic models in MEDLINE, CINAHL Plus and the Cochrane Library—CENTRAL. The primary outcome was representation of multimorbidity or frailty. The secondary outcome was predictive accuracy of identified models in relation to presence of multimorbidity or frailty.ResultsNinety-seven studies reporting 121 different kidney failure prognostic models were identified. Two studies reported prevalence of multimorbidity and a single study reported prevalence of frailty. The rates of specific comorbidities were reported in a greater proportion of studies: 67.0% reported baseline data on diabetes, 54.6% reported hypertension and 39.2% reported cardiovascular disease. No studies included frailty in model development, and only one study considered multimorbidity as a predictor variable. No studies assessed model performance in populations in relation to multimorbidity. A single study assessed associations between frailty and the risks of kidney failure and death.ConclusionsThere is a paucity of kidney failure risk prediction models that consider the impact of multimorbidity and/or frailty, resulting in a lack of clear evidence-based practice for multimorbid or frail individuals. These knowledge gaps should be explored to help clinicians know whether these models can be used for CKD patients who experience multimorbidity and/or frailty.Systematic review registrationThis review has been registered on PROSPERO (CRD42022347295).

Acetazolamide Therapy and Kidney Function in Persons with Nonalbuminuric Diabetes Mellitus Type 1.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower the risk of kidney failure in persons with type 2 diabetes. The presumed mechanism of action is through greater delivery of sodium to the distal tubule, activation of tubuloglomerular feedback which lowers glomerular filtration rate (GFR) and intra-glomerular pressure. SGLT2is are not approved for use in persons with type 1 diabetes due to the risk of diabetic ketoacidosis. Acetazolamide, a proximal tubule diuretic, delivers more sodium to the distal nephron, and may activate tubuloglomerular feedback in a similar way to SGLT2is without a higher risk of diabetic ketoacidosis. The kidney effects and safety of acetazolamide in persons with type 1 diabetes have not been well studied. Methods: We conducted a dose-escalation trial to determine the effects of 3 dosages of oral acetazolamide (62.5mg, 125mg, and 250mg, all twice-daily) in 12 persons with type 1 diabetes. Participants were treated for 2 weeks followed by a 2-week washout before exposure to the next dosage level. Blood and urine chemistries, as well as iohexol measured GFR, were assessed before and after each treatment interval. We aimed to identify a dose that maximized measured GFR reductions while minimizing adverse effects. Results: The mean age was 46±17 years, 100% were White, and 75% were female. The mean measured GFR was 89±18ml/min/1.73m2 at baseline. Acetazolamide reduced measured GFR by 15% (95% CI 9, 21), 14% (95% CI 7, 21), and 15% (95% CI 10, 21) after 2 weeks at the 62.5mg, 125mg, and 250mg twice-daily dosage levels respectively. The measured GFR reduction was fully reversed after each 2-week washout. Serum bicarbonate was reduced by 2.3, 4.2 and 4.4 mEq/L with escalating doses, and no episodes of hypokalemia (&lt; 3.5 mEq/L) were observed. Conclusions: Among persons with type 1 diabetes and preserved kidney function, acetazolamide caused an acute, reversible reduction in measured GFR without effects on glucose metabolism.

A-201 The Impact of Implementing the CKD-EPI 2021 Equation for Calculation of Estimated Glomerular Filtration Rate (eGFR) and the Kidney Failure Risk Equation (KFRE) on a Large Community Laboratory Population

Abstract Background Community laboratories in Ontario, Canada have reported estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009 equation without race adjustment since 2020. In 2023, the Canadian Society of Nephrology recommended implementation of the CKD-EPI 2021 equation for eGFR, which does not incorporate a race-based modifier. Community laboratories will also report the 5-year Kidney Failure Risk Equation (KFRE), a risk prediction model to estimate the risk of renal failure in people with chronic kidney disease (CKD) Stages 3 to 5 (eGFR &amp;lt;60 mL/min/1.73m2), which is more accurate than judging by eGFR alone. This study assessed the impact of implementing the CKD-EPI 2021 equation for eGFR and the 5-year KFRE in a large community laboratory population. Methods Laboratory results for serum creatinine and urine albumin to creatinine ratio (ACR), patient sex and age were extracted from Dynacare’s laboratory information system for November 2023. The CKD-EPI 2009 without race adjustment and the CKD-EPI 2021 were calculated. Reclassification of CKD stage using the CKD-EPI 2021 equation was assessed. The 4-variable 5-year KFRE was calculated for patients in CKD Stage 3-5 (eGFR &amp;lt;60 mL/min/1.73m2) when all parameters including, patient age, sex, creatinine and ACR, were available. Results Data was extracted for 242,843 patients. The median age was 61 years old and 47% of the population was female. The calculated median eGFR was 83 and 87 mL/min/1.73m2 when the CKD-EPI 2009 with no race adjustment, and CKD-EPI 2021 equation, respectively, were applied. Linear regression analysis showed a correlation of 0.997 with a slope of 0.990 and y-intercept of 4.513. A total of 13.0% (n=31,679) of patients were reclassified into a less progressive CKD stage when the CKD-EPI 2021 was applied compared to the CKD-EPI 2009 without race adjustment. Notable, was the reclassification of 21.8% (n=6899) of those patients from Stage 3a to 2, i.e. patients no longer have CKD (eGFR &amp;gt;60 mL/min/1.73m2) based on the new calculation. 64.8% (n=20513) of patients were reclassified from Stage 2 to 1, 9.4% (n=2977) were reclassified from Stage 3b to 3a, 3.5% (n=1102) were classified from Stage 4 to 3b, and 0.6% (n=188) were reclassified from Stage 5 to 4. The 5-year KFRE was calculated when creatinine and ACR were included on the same order and the patient was classified as Stage 3 to 5 (n=12,737 patients with eGFR &amp;lt;60 mL/min/1.73m2). The 5-year KFRE showed increasing median risk, 1%, 4%, 27%, 95%, as CKD stage increased from 3a, 3b, 4 and 5, respectively. 1.1% (n=58) of patients in Stage 3a, 43.3% (n=1584) of patients in Stage 3b, 96.6% (n=1994) of patients in Stage 4, and 100% (n=401) of patients in Stage 5 met the KFRE threshold of ≥5% for referral to nephrology. Conclusions Implementation of the CKD-EPI 2021 resulted in reclassification to a less progressive CKD stage. Use of the KFRE as a clinical decision tool will increase patient referral to nephrology. This study provided insight into the impact of the implementation of the CKD-EPI 2021 and KFRE and highlights the underutilization of ACR in a community population.

Exploration of patients’ and healthcare professionals’ perspectives on kidney failure risk and the use of the kidney failure risk equation in MULTIPle lOng-term condItions aNd frailTy (MULTIPOINT) study: a qualitative interview and focus group study protocol

IntroductionClinical guidelines recommend the use of the kidney failure risk equation (KFRE) to guide the referral of individuals with chronic kidney disease (CKD) to secondary kidney care services. People living...

Impact of DNA Methylation Variation on Risk of Kidney Failure in Type 1 Diabetes Is Mediated through Increased Levels of Circulating Proteins

Impact of DNA Methylation Variation on Risk of Kidney Failure in Type 1 Diabetes Is Mediated through Increased Levels of Circulating Proteins

Anti-phospholipid antibodies nephropathy is associated with an increased risk of kidney failure: a systematic literature review and meta-analysis.

Anti-phospholipid antibodies nephropathy (aPL-N) is a complex feature of anti-phospholipid syndrome due to microvascular lesions. Renal prognosis and predictors of outcome are not yet known. We performed a systematic review of the literature (February 2006-January 2024) using the PubMed, Scopus, Cochrane Library and EMBASE databases. Two reviewers independently conducted literature screening and data extraction in a blinded, standardized manner. A random effects model was used to pool odds ratios (ORs) [with 95% confidence interval (CI)] for the primary analysis, the risk of kidney failure. Subgroup analyses were performed for clinical and laboratory features that predicted renal outcomes. Heterogeneity was assessed by I2. Six records involving 709 patients were included in the meta-analysis. Biopsy-proven aPL-N was found in 238/832 (28.6%) patients. Acute kidney injury (AKI) was present at diagnosis in 20/65 (30.8%), while 73/233 (31.3%) patients with aPL-N developed chronic kidney disease (CKD)/end-stage kidney disease (ESKD) at follow-up. aPL-N was associated with an increased risk of CKD/ESKD [OR 6.89 (95% CI 2.42-19.58)] and AKI [OR 2.97 (95% CI 1-4-6.29)]. Arterial hypertension and positivity for lupus anticoagulant, anti-cardiolipin antibodies and anti-β2 glycoprotein I antibodies were associated with an increased risk of developing aPL-N [OR 3.7 (95% CI 1.9-7.23), OR 4.01 (95% CI 1.88-8.53), OR 2.35 (95% CI 1.31-4.21) and OR 19.2 (95% CI 2.91-125.75), respectively]. aPL-N is associated with poor renal outcomes. High blood pressure and aPL positivity have been identified as predictors of adverse renal outcomes. This up-to-date knowledge on renal outcomes and predictors of renal outcomes in aPL-N enables a personalized follow-up and therapeutic approach.

Periodontal Disease, Its Treatment, and the Risk of Kidney Failure among US Veterans

Periodontal Disease, Its Treatment, and the Risk of Kidney Failure among US Veterans

The potential adverse effects of hypodermic glucagon-like peptide -1 receptor agoniston patients with type 2 diabetes: A population-based study.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long-term safety of GLP-1 RAs remains insufficiently studied. This study aimed to provide real-world evidence on potential adverse outcomes associated with GLP-1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. We conducted a retrospective cohort study involving 7746 T2D patients on GLP-1 RAs in Shenzhen, China. They were compared with 124 371 metformin-only users and 36 146 insulin-only users, forming two therapy control groups. GLP-1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP-1 RAs use. Compared with metformin-only users, GLP-1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24-3.24), acute nephritis (3.20, 2.17-4.70), kidney failure (3.73, 2.74-5.08), thyroid cancer (2.25, 1.23-4.10), and thyroid dysfunction (1.27, 1.00-1.63), respectively; Similar results were also found when compared with insulin-only users. Importantly, long-term (≥12 months) GLP-1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. Compared with traditional T2D treatments, GLP-1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP-1 RAs. Further validation is crucial across diverse populations.

Concomitant Wilms tumor and autosomal dominant polycystic kidney disease.

Concomitant Wilms tumor (WT) and autosomal dominant polycystic kidney disease (ADPKD) is exceedingly rare, presenting a diagnostic and technical challenge to pediatric surgical oncologists. The simultaneous workup and management of these disease processes are incompletely described. We performed a retrospective analysis of patients treated at our institution with concomitant diagnoses of WT and ADPKD. We also review the literature on the underlying biology and management principles of these conditions. We present three diverse cases of concomitant unilateral WT and ADPKD who underwent nephrectomy. One patient had preoperative imaging consistent with ADPKD with confirmatory testing postoperatively, one was found to have contralateral renal cysts intraoperatively with confirmatory imaging post nephrectomy, and one was diagnosed in childhood post nephrectomy. All patients are alive at last follow-up, and the patient with longest follow-up has progressed to end-stage kidney failure requiring transplantation and dialysis in adulthood. All patients underwent germline testing and were found to have no cancer predisposition syndrome or pathogenic or likely pathogenic variants for WT. Concomitant inheritance of ADPKD and development of WT are extremely rare, and manifestations of ADPKD may not present until late childhood or adulthood. ADPKD is not a known predisposing condition for WT. When ADPKD diagnosis is made by family history, imaging, and/or genetic testing before WT diagnosis and treatment, the need for extensive preoperative characterization of cystic kidney lesions in children and increased risk of post-nephrectomy kidney failure warrant further discussion of surgical approach and perioperative management strategies.

Competing Risks of Kidney Failure and Death by Baseline eGFR in Diabetes

Competing Risks of Kidney Failure and Death by Baseline eGFR in Diabetes