Faculty Bibliography

People with type 2 diabetes and chronic kidney disease have a high risk for kidney failure and cardiovascular (CV) complications. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2i) independently reduce CV and kidney events. The effect of combining both is unclear. FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo. The primary outcome was a composite of kidney failure, ≥50% estimated glomerular filtration rate reduction, kidney death or CV death. The risk of the primary outcome was 24% lower in all participants treated with semaglutide versus placebo (95% confidence interval: 34%, 12%). The primary outcome occurred in 41/277 (semaglutide) versus 38/273 (placebo) participants on SGLT2i at baseline (hazard ratio 1.07; 95% confidence interval: 0.69, 1.67; P = 0.755) and in 290/1,490 versus 372/1,493 participants not taking SGLT2i at baseline (hazard ratio 0.73; 0.63, 0.85; P < 0.001; P interaction 0.109). Three confirmatory secondary outcomes were predefined. Treatment differences favoring semaglutide for total estimated glomerular filtration rate slope (ml min^-1/1.73 m²/year) were 0.75 (-0.01, 1.5) in the SGLT2i subgroup and 1.25 (0.91, 1.58) in the non-SGLT2i subgroup, P interaction 0.237. Semaglutide benefits on major CV events and all-cause death were similar regardless of SGLT2i use (P interaction 0.741 and 0.901, respectively). The benefits of semaglutide in reducing kidney outcomes were consistent in participants with/without baseline SGLT2i use; power was limited to detect smaller but clinically relevant effects. ClinicalTrials.gov identifier: NCT03819153 .

AIM/OBJECTIVE:To explore the effect of canagliflozin on kidney and cardiovascular events and safety outcomes in individuals with type 2 diabetes and chronic kidney disease across geographic regions and racial groups. MATERIALS AND METHODS/METHODS:A stratified Cox proportional hazards model was used to assess efficacy and safety outcomes by geographic region and racial group. The primary composite outcome was a composite of end-stage kidney disease (ESKD), doubling of the serum creatinine (SCr) level, or death from kidney or cardiovascular causes. Secondary outcomes included: (i) cardiovascular death or heart failure (HF) hospitalization; (ii) cardiovascular death, myocardial infarction (MI) or stroke; (iii) HF hospitalization; (iv) doubling of the SCr level, ESKD or kidney death; (v) cardiovascular death; (vi) all-cause death; and (vii) cardiovascular death, MI, stroke, or hospitalization for HF or for unstable angina. RESULTS:The 4401 patients were divided into six geographic region subgroups: North America (n = 1182, 27%), Central and South America (n = 941, 21%), Eastern Europe (n = 947, 21%), Western Europe (n = 421, 10%), Asia (n = 749, 17%) and Other (n = 161, 4%). The analyses included four racial groups: White (n = 2931, 67%), Black or African American (n = 224, 5%), Asian (n = 877, 20%) and Other (n = 369, 8%). Canagliflozin reduced the relative risk of the primary composite outcome in the overall trial by 30% (hazard ratio 0.70, 95% confidence interval 0.59-0.82; P = 0.00001). Across geographic regions and racial groups, canagliflozin consistently reduced the primary composite endpoint without evidence of heterogeneity (interaction P values of 0.39 and 0.91, respectively) or significant safety outcome differences. CONCLUSIONS:Canagliflozin reduces the risk of kidney and cardiovascular events similarly across geographic regions and racial groups.

The risk of arrhythmia and its management become increasingly complex as kidney disease progresses. This presents a multifaceted clinical challenge. Our discussion addresses these specific challenges relevant to patients as their kidney disease advances. We highlight numerous opportunities for enhancing the current standard of care within this realm. Additionally, this review delves into research concerning early detection, prevention, diagnosis, and treatment of various arrhythmias spanning the spectrum of kidney disease.

BACKGROUND:Chronic kidney disease (CKD) is highly prevalent, affecting approximately 11% of U.S. adults. Multiple studies have evaluated a potential association between CKD and urinary tract malignancies. Summary estimates of urinary tract malignancy risk in CKD patients with and without common co-existing conditions may guide clinical practice recommendations. METHODS:Four electronic databases were searched for original cohort studies evaluating the association between CKD and urinary tract cancers (kidney cancer and urothelial carcinoma) through May 25, 2023, in persons with at least moderate CKD and no dialysis or kidney transplantation. Quality assessment was performed for studies meeting inclusion criteria using the Newcastle-Ottawa Scale. Meta-analysis with a random-effects model was performed for unadjusted incidence rate ratios (IRR) as well as adjusted hazard ratios (aHR) for confounding conditions (diabetes, hypertension, and/or tobacco use), shown to have association with kidney cancer and urothelial carcinoma. Sub-analysis was conducted for estimates associated with CKD stages separately. RESULTS:Six cohort studies with 8 617 563 persons were included. Overall, methodological quality of the studies was good. CKD was associated with both higher unadjusted incidence and adjusted hazard of kidney cancer (IRR, 3.36; 95% confidence interval [CI], 2.32-4.88; aHR, 2.04; 95% CI, 1.77-2.36) and urothelial cancer (IRR, 3.96; 95% CI, 2.44-6.40; aHR, 1.40; 95% CI, 1.22-1.68) compared with persons without CKD. Examining incident urinary tract cancers by CKD severity, risks were elevated in stage 3 CKD (kidney aHR, 1.89; 95% CI, 1.56-2.30; urothelial carcinoma aHR, 1.40; 95% CI, 1.18-1.65) as well as in stages 4/5 CKD (kidney cancer aHR, 2.30; 95% CI, 2.00-2.66, UC aHR, 1.24; 95% CI, 1.04-1.49). CONCLUSIONS:Even moderate CKD is associated with elevated risk of kidney cancer and UC. Providers should consider these elevated risks when managing individuals with CKD, particularly when considering evaluation for the presence and etiology of hematuria.

BACKGROUND:Chronic kidney disease (CKD) has been implicated as a risk factor for venous thromboembolism, but the evidence is limited to relatively healthy populations. The objective of the current study was to discern whether parameters of kidney function and damage are associated with the occurrence of venous thromboembolism after hospitalization. METHODS:We conducted a retrospective study including 23,899 and 11,552 adult individuals hospitalized within Geisinger Health System and NYU Langone Health from 2004 to 2019 and 2012 to 2022, respectively. A Poisson model was used to evaluate adjusted incidence rates of venous thromboembolism according to estimated glomerular filtration rate (eGFR) and albuminuria categories in each cohort. Cox proportional hazards models were used to analyze associations of eGFR and urinary albumin to creatinine ratio (UACR) with venous thromboembolism and hazard ratios were meta-analyzed across cohorts. RESULTS:Both lower eGFR and higher UACR were associated with higher risks of venous thromboembolism. In the Geisinger cohort, the incidence of venous thromboembolism after hospital discharge ranged from 10.7 (95% CI 9.2 - 12.6) events per 1000 person-years in individuals in G1A1 (eGFR >90 mL/min/1.73 m2 and UACR <30 mg/g) to 27.7 (95% CI 20.6 - 37.2) events per 1000 person-years in individuals with G4-5A3 (eGFR <30 mL/min/1.73 m2 and UACR >300 mg/g). A similar pattern was observed in the NYU cohort. Meta-analyses of the two cohorts showed that every 10 mL/min/1.73m2 reduction in eGFR below 60 mL/min/1.73m2 was associated with a 6% higher risk of venous thromboembolism (HR 1.06 [1.02 - 1.11], P = 0.01), and each two-fold higher UACR was associated with a 5% higher risk of venous thromboembolism (HR 1.05 [1.03 - 1.07], P <0.001). CONCLUSIONS:Both eGFR and UACR were independently associated with higher risk of venous thromboembolism after hospitalization. The incidence rate was higher with greater severity of CKD.

RATIONALE & OBJECTIVE/UNASSIGNED:Conservative kidney management (CKM) is a viable treatment option for many patients with chronic kidney disease. However, CKM practices and resources in the United States are not well described. We undertook this study to gain a better understanding of factors influencing uptake of CKM by describing: (1) characteristics of patients who choose CKM, (2) provider practice patterns relevant to CKM, and (3) CKM resources available to providers. STUDY DESIGN/UNASSIGNED:Cross-sectional study. SETTING & PARTICIPANTS/UNASSIGNED:(n=1018) and available information on whether a decision had been made to pursue CKM at the time of kidney failure, patient (n=407) reports of discussions about forgoing dialysis, and provider (n=26) responses about CKM delivery and available resources in their health systems. ANALYTICAL APPROACH/UNASSIGNED:Descriptive statistics were used to report patient demographics, clinical information, provider demographics, and clinic characteristics. RESULTS/UNASSIGNED:Among data from 1018 patients, 68 (7%) were recorded as planning for CKM. These patients were older, had more comorbidities, and were more likely to require assistance with transfers. Of the 407 patient surveys, 18% reported a conversation about forgoing dialysis with their nephrologist. A majority of providers felt comfortable discussing CKM; however, no clinics had a dedicated clinic or protocol for CKM. LIMITATIONS/UNASSIGNED:Inconsistent survey terminology and unlinked patient and provider responses. CONCLUSIONS/UNASSIGNED:Few patients reported discussion of forgoing dialysis with their providers and even fewer anticipated a choice of CKM on reaching kidney failure. Most providers were comfortable discussing CKM, but practiced in clinics that lacked dedicated resources. Further research is needed to improve the implementation of a CKM pathway. PLAIN-LANGUAGE SUMMARY/UNASSIGNED:For older comorbid adults with kidney failure, conservative kidney management (CKM) can be an appropriate treatment choice. CKM is a holistic approach with treatment goals of maximizing quality of life and preventing progression of chronic kidney disease (CKD) without initiation of dialysis. We investigated US CKM practices and found that among 1018 people with CKD, only 7% were planning for CKM. Of 407 surveyed patients, 18% reported a conversation with their provider about forgoing dialysis. In contrast, most providers felt comfortable discussing CKM; however, none reported working in an environment with a dedicated CKM clinic or protocol. Our data show the need for further CKM education in the United States as well as dedicated resources for its delivery.