Evaluation of Risk Data in 4.5 Million Patients for Implementing New Guidelines for Kidney Function Reporting

Background: Clinical guidelines recommend reporting estimated glomerular filtration rate (eGFR) from serum creatinine measurements using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, still organizations report eGFR mainly using alternative equations. Objective: To evaluate the risk relationship of eGFR from the CKD-EPI equation relative to the Modification of Diet in Renal Disease (MDRD) and Mayo Clinic Quadratic (MCQ), describe differences in interpretation of eGFR values, and implications associated with switching to the CKD-EPI equation, in a large patient population receiving ambulatory care in the United States. Results: Overall, 4.5 million patients aged 18–99 were included in the study, with 37,000 events for ESRD and 195,000 for all-cause mortality. The average eGFR was considerably lower for CKD-EPI (82.7 ml/min/1.73m2) and MDRD (79.7 ml/min/1.73m2), compared to MCQ (94.9 ml/min/1.73m2). Accordingly, the prevalence of GFR category 3–5 (<60 mL/min/1.73 m²) was 15.8% with CKD-EPI, 17.3% with MDRD, and 6.4% with MCQ. The CKD-EPI equation had a similarly steep risk gradient to the MDRD equation in GFR 3-5 range, both steeper than the risk gradient for the MCQ equation. The risk gradient at higher estimates of GFR was steeper for the CKD-EPI equation relative to MDRD, but shallower than MCQ. The CKD-EPI equation, compared to MDRD, reclassified more patients upward to higher categories of eGFR (2.6% downward vs.15.7% upward), and many more patients downward to lower categories compared to the MCQ (39.1% downward vs. 1.3% upward). Net reclassification improvement favored the CKD-EPI to MDRD equation for ESRD (0.12) and all-cause mortality (0.19), and favored the CKD-EPI to MCQ for all-cause mortality (0.06) but not ESRD (‒ 0.07). Conclusion: Regarding risk stratification, the recommended CKD-EPI equation is superior to MDRD. Similar estimates of GFR from the two equations, especially in GFR 3–5 range, facilitate transitioning to the CKD-EPI equation from MDRD. MCQ largely shifted the distribution of eGFR and eGFR-risk relationship to higher levels of eGFR, warranting its careful interpretation particularly at referral or transition from or to facilities using other equations

Albuminuria Testing in Hypertension and Diabetes:An Individual-Participant Data Meta-Analysis in a Global Consortium

Albuminuria is an under-recognized component of chronic kidney disease definition, staging, and prognosis. Guidelines, particularly for hypertension, conflict on recommendations for urine albumin-to-creatinine ratio (ACR) measurement. Separately among 1 344 594 adults with diabetes and 2 334 461 nondiabetic adults with hypertension from the chronic kidney disease Prognosis Consortium, we assessed ACR testing, estimated the prevalence and incidence of ACR ≥30 mg/g and developed risk models for ACR ≥30 mg/g. The ACR screening rate (cohort range) was 35.1% (12.3%-74.5%) in diabetes and 4.1% (1.3%-20.7%) in hypertension. Screening was largely unrelated to the predicted risk of prevalent albuminuria. The median prevalence of ACR ≥30 mg/g across cohorts was 32.1% in diabetes and 21.8% in hypertension. Higher systolic blood pressure was associated with a higher prevalence of albuminuria (odds ratio [95% CI] per 20 mm Hg in diabetes, 1.50 [1.42-1.60]; in hypertension, 1.36 [1.28-1.45]). The ratio of undetected (due to lack of screening) to detected ACR ≥30 mg/g was estimated at 1.8 in diabetes and 19.5 in hypertension. Among those with ACR/g, the median 5-year incidence of ACR ≥30 mg/g across cohorts was 23.9% in diabetes and 21.7% in hypertension. Incident albuminuria was associated with initiation of renin-angiotensin-aldosterone system inhibitors (incidence-rate ratio [95% CI], diabetes 3.09 [2.71-3.53]; hypertension 2.87 [2.29-3.59]). In conclusion, despite similar risk of albuminuria to those with diabetes, ACR screening in patients with hypertension was low. Our findings suggest that regular albuminuria screening should be emphasized to enable early detection of chronic kidney disease and initiation of treatment with cardiovascular and renal benefits

The kidney failure risk equation:evaluation of novel input variables including eGFR estimated using the CKD-EPI 2021 equation in 59 cohorts

SIGNIFICANCE STATEMENT: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities. BACKGROUND: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 . METHODS: Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death. RESULTS: The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall. CONCLUSIONS: The original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2 when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant–Based Meta-analysis

Financial Support: The CKD-PC Data Coordinating Center is funded in part by a program grant from the U.S. National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100446). Various sources have supported enrollment and data collection, including laboratory measurements and follow-up, in the collaborating cohorts of the CKD-PC. These funding sources include government agencies, such as national institutes of health and medical research councils, as well as the foundations and industry sponsors listed in Supplemental Appendix 3 (available at Annals.org).Peer reviewedPostprin

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

Evaluation of Risk Data in 4.5 Million Patients for Implementing New Guidelines for Kidney Function Reporting

Background: Clinical guidelines recommend reporting estimated glomerular filtration rate (eGFR) from serum creatinine measurements using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, still organizations report eGFR mainly using alternative equations. Objective: To evaluate the risk relationship of eGFR from the CKD-EPI equation relative to the Modification of Diet in Renal Disease (MDRD) and Mayo Clinic Quadratic (MCQ), describe differences in interpretation of eGFR values, and implications associated with switching to the CKD-EPI equation, in a large patient population receiving ambulatory care in the United States. Results: Overall, 4.5 million patients aged 18–99 were included in the study, with 37,000 events for ESRD and 195,000 for all-cause mortality. The average eGFR was considerably lower for CKD-EPI (82.7 ml/min/1.73m2) and MDRD (79.7 ml/min/1.73m2), compared to MCQ (94.9 ml/min/1.73m2). Accordingly, the prevalence of GFR category 3–5 (<60 mL/min/1.73 m²) was 15.8% with CKD-EPI, 17.3% with MDRD, and 6.4% with MCQ. The CKD-EPI equation had a similarly steep risk gradient to the MDRD equation in GFR 3-5 range, both steeper than the risk gradient for the MCQ equation. The risk gradient at higher estimates of GFR was steeper for the CKD-EPI equation relative to MDRD, but shallower than MCQ. The CKD-EPI equation, compared to MDRD, reclassified more patients upward to higher categories of eGFR (2.6% downward vs.15.7% upward), and many more patients downward to lower categories compared to the MCQ (39.1% downward vs. 1.3% upward). Net reclassification improvement favored the CKD-EPI to MDRD equation for ESRD (0.12) and all-cause mortality (0.19), and favored the CKD-EPI to MCQ for all-cause mortality (0.06) but not ESRD (‒ 0.07). Conclusion: Regarding risk stratification, the recommended CKD-EPI equation is superior to MDRD. Similar estimates of GFR from the two equations, especially in GFR 3–5 range, facilitate transitioning to the CKD-EPI equation from MDRD. MCQ largely shifted the distribution of eGFR and eGFR-risk relationship to higher levels of eGFR, warranting its careful interpretation particularly at referral or transition from or to facilities using other equations

Burden of Herpes Zoster Among Patients with Psoriasis in the United States

Abstract Introduction Patients with psoriasis (PsO) are at increased risk of herpes zoster (HZ), but recent data on the incidence of HZ among patients with PsO and the impact of HZ on healthcare resource use (HRU) and costs for patients with PsO have not been described. Methods This retrospective, longitudinal, cohort study estimated HZ incidence in cohorts of adults with vs without PsO (PsO + vs PsO–) and HRU and costs among those with PsO, with vs without HZ (PsO + /HZ + vs PsO + /HZ–) using Optum’s de-identified Clinformatics Data Mart Database during 2015–2020. Patients with psoriatic arthritis were excluded from all four cohorts. Comparisons between cohorts used generalized linear models to adjust outcomes based on various baseline characteristics. Results The incidence rate of HZ was significantly higher in the PsO + (n = 144,115) vs PsO– (n = 23,837,237) cohorts at 11.35 vs 7.67 per 1000 patient-years; adjusted incidence rate ratio (aIRR): 1.21, 95% confidence interval (CI): 1.16–1.25. HRU (outpatient, emergency department, and inpatient) was significantly higher in the PsO + /HZ + (n = 1859) vs PsO + /HZ– (n = 78,664) cohorts during 1 month and 3 months after HZ diagnosis (e.g., outpatient visits during month: 2.83 vs 1.30 per patient; aIRR: 1.96; 95% CI 1.86–2.06). Mean all-cause costs were also significantly higher in the PsO + /HZ + vs PsO + /HZ– cohort during both month ($5020 vs$2715 per patient; adjusted cost difference: $1390; 95$842–$1964) and 3 months ($12,305 vs $8256; adjusted cost difference:$1422; 95% CI $280–$2889) after HZ diagnosis. Conclusion These findings show the increased incidence of HZ among patients with PsO and the clinical and economic burdens of HZ in this population. Considering the high prevalence of PsO, insights into the impact of HZ in these patients provide valuable evidence to inform clinical decision-making. Graphical abstrac

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis

International audienceBACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundati

Change in albuminuria and subsequent risk of end-stage kidney disease : an individual participant-level consortium meta-analysis of observational studies

US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.Peer reviewedPostprintPostprin