Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies.

Data for the association of sex with chronic kidney disease (CKD) progression are conflicting, a relationship this study sought to examine. Pooled analysis of 4 Italian observational cohort studies. 1,311 older men and 1,024 older women with estimated glomerular filtration rate (eGFR)<45mL/min/1.73m2 followed up in renal clinics. Sex. End-stage kidney disease (ESKD), defined as maintenance dialysis or kidney transplantation, as the primary outcome; all-cause mortality and eGFR decline as secondary outcomes. Cox proportional hazard analysis to estimate the relative risk for ESKD and mortality and linear mixed models to estimate the rate of eGFR decline. Age, systolic blood pressure, and use of renin-angiotensin system inhibitors were similar in men and women. Baseline eGFRs were 27.6±10.2 in men and 26.0±10.6mL/min/1.73m2 in women (P<0.001), while median proteinuria was lower in women (protein excretion, 0.45 [IQR, 0.14-1.10] g/d) compared with men (0.69 [IQR 0.19-1.60] g/d; P<0.001). During a median follow-up of 4.2 years, 757 developed ESKD (59.4% men) and 471 died (58.4% men). The adjusted risks for ESKD and mortality were higher in men (HRs of 1.50 [95% CI, 1.28-1.77] and 1.30 [95% CI, 1.06-1.60], respectively). This finding was consistent across CKD stages. We observed a significant interaction between sex and proteinuria, with the risk for ESKD in men being significantly greater than for women at a level of proteinuria of ∼0.5g/d or greater. The slope of decline in eGFR was steeper in men (-2.09; 95% CI, -2.21 to-1.97mL/min/1.73m2 per year) than in women (-1.79; 95% CI, -1.92 to-1.66mL/min/1.73m2 per year; P<0.001). Although sex differences in eGFR decline were not different across CKD stages (P=0.3), the difference in slopes between men and women was progressively larger with proteinuria >0.5g/d (P = 0.04). Residual confounding; only whites were included. Excess renal risk in men may, at least in part, be related to higher levels of proteinuria in men compared with women.

Minutolo R ，Gabbai FB ，Chiodini P ，Provenzano M ，Borrelli S ，Garofalo C ，Bellizzi V ，Russo D ，Conte G ，De Nicola L ，Collaborative Study Group on the Conservative Treatment of CKD of the Italian Society of Nephrology ... -  《-》

Risk of Progression of Nonalbuminuric CKD to End-Stage Kidney Disease in People With Diabetes: The CRIC (Chronic Renal Insufficiency Cohort) Study.

Reduced glomerular filtration rate (GFR) in the absence of albuminuria is a common manifestation of chronic kidney disease (CKD) in diabetes. However, the frequency with which it progresses to end-stage kidney disease (ESKD) is unknown. Multicenter prospective cohort study. We included 1,908 participants with diabetes and reduced GFR enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. Urinary albumin and protein excretion. Incident ESKD, CKD progression (ESKD or ≥50% reduction in estimated GFR [eGFR] from baseline), and annual rate of decline in kidney function. ESKD was ascertained by self-report and by linkage to the US Renal Data System. We used Cox proportional hazards modeling to estimate the association of albuminuria and proteinuria with incident ESKD or CKD progression and linear mixed-effects models to assess differences in eGFR slopes among those with and without albuminuria. Mean eGFR at baseline was 41.2mL/min/1.73m2. Normal or mildly increased 24-hour urinary albumin excretion (<30mg/d) at baseline was present in 28% of participants, but in only 5% of those progressing to ESKD. For those with baseline normal or mildly increased albuminuria, moderately increased albuminuria (albumin excretion, 30-299mg/d), and 2 levels of severely increased albuminuria (albumin excretion, 300-999 and ≥1,000mg/d): crude rates of ESKD were 7.4, 34.8, 78.7, and 178.7 per 1,000 person-years, respectively; CKD progression rates were 17.0, 61.4, 130.5, and 295.1 per 1,000 person-years, respectively; and annual rates of eGFR decline were -0.17, -1.35, -2.74, and -4.69mL/min/1.73m2, respectively. We were unable to compare the results with healthy controls. In people with diabetes with reduced eGFRs, the absence of albuminuria or proteinuria is common and carries a much lower risk for ESKD, CKD progression, or rapid decline in eGFR compared with those with albuminuria or proteinuria. The rate of eGFR decline in normoalbuminuric CKD was similar to that reported for the general diabetic population.

Koye DN ，Magliano DJ ，Reid CM ，Jepson C ，Feldman HI ，Herman WH ，Shaw JE ... -  《-》

CKD Progression and Mortality Among Men and Women: A Nationwide Study in Sweden.

Chronic kidney disease (CKD) is a global health problem with increasing prevalence. Several sex-specific differences have been reported for disease progression and mortality. Selection and survival bias might have influenced the results of previous cohort studies. The objective of this study was to investigate sex-specific differences of CKD progression and mortality among patients with CKD not receiving maintenance dialysis. Observational cohort study. Adult patients with incident CKD glomerular filtration rate categories 3b to 5 (G3b-G5) identified between 2010 and 2018 within the nationwide Swedish Renal Registry-CKD (SRR-CKD). Sex. Time to CKD progression (defined as a change of at least 1 CKD stage or initiation of kidney replacement therapy [KRT]) or death. Repeated assessments of estimated glomerular filtration rate (eGFR). CKD progression and mortality before KRT were assessed by the cumulative incidence function methods and Fine and Gray models, with death handled as a competing event. Sex differences in eGFR slope were estimated using mixed effects linear regression models. 7,388 patients with incident CKD G3b, 18,282 with incident CKD G4, and 9,410 with incident CKD G5 were identified. Overall, 19.6 (95% CI, 19.2-20.0) patients per 100 patient-years progressed, and 10.1 (95% CI, 9.9-10.3) patients per 100 person-years died. Women had a lower risk of CKD progression (subhazard ratio [SHR], 0.88 [95% CI, 0.85-0.92]), and a lower all-cause (SHR, 0.90 [95% CI, 0.85-0.94]) and cardiovascular (SHR, 0.83 [95% CI, 0.76-0.90]) mortality risk. Risk factors related to a steeper decline in eGFR included age, sex, albuminuria, and type of primary kidney disease. Incomplete data for outpatient visits and laboratory measurements and regional differences in reporting. Compared to women, men had a higher rate of all-cause and cardiovascular mortality, an increased risk of CKD progression, and a steeper decline in eGFR.

Swartling O ，Rydell H ，Stendahl M ，Segelmark M ，Trolle Lagerros Y ，Evans M ... -  《-》

Estimating Time to ESRD in Children With CKD.

The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development. Observational cohort study. Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry. A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m2. eGFR was estimated using the CKiD-derived "bedside" equation. Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to amalgamate levels of similar risk. Among 1,232 children, median age was 12 (IQR, 8-15) years, median eGFR was 47 (IQR, 33-62) mL/min/1.73m2, 60% were males, and 13% had UPCRs>2.0mg/mg at study entry. 6 ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44, and 15-29mL/min/1.73m2) and UPCR categories (<0.5, 0.5-2.0, and >2.0mg/mg) described the risk continuum. Median times to event ranged from longer than 10 years for eGFRs of 45 to 90mL/min/1.73m2 and UPCRs<0.5mg/mg to 0.8 years for eGFRs of 15 to 30mL/min/1.73m2 and UPCRs>2mg/mg. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the 10 subsample validation models. Observational study, used cross-validation rather than external validation. CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.

Furth SL ，Pierce C ，Hui WF ，White CA ，Wong CS ，Schaefer F ，Wühl E ，Abraham AG ，Warady BA ，Chronic Kidney Disease in Children (CKiD) ，Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) Study Investigators ... -  《-》

Estimated GFR at Dialysis Initiation and Mortality in Children and Adolescents.

The association of estimated glomerular filtration rate (eGFR) at dialysis therapy initiation with mortality among adult dialysis patients has been greatly debated, with some studies showing no benefit from early dialysis therapy initiation. However, this association has not been well investigated in pediatric dialysis patients. The objective of this study was to evaluate the mortality risk associated with eGFR at dialysis therapy initiation in children and adolescents with kidney failure. Retrospective cohort study. 9,963 incident dialysis patients aged 1 to 17 years in the US Renal Data System registry (1995-2016). eGFRs at dialysis therapy initiation calculated using the pediatric-specific bedside Schwartz equation (<5, 5-<7, 7-<9, 9-<12, and ≥12mL/min/1.73m2). Time to all-cause death. Cox proportional hazards regression adjusted for case-mix variables, height, body mass index, hemoglobin level, and serum albumin level. Median eGFR was 7.8 (IQR, 5.6-10.5) mL/min/1.73m2 and median age was 13 (IQR, 9-16) years. 696 deaths were observed during the median follow-up of 1.4 (IQR, 0.7-2.7) years, and overall crude mortality rate was 31 per 1,000 patient-years. There appeared to be a trend toward higher mortality risk across higher eGFRs at dialysis therapy initiation. Compared with eGFRs of 7 to <9mL/min/1.73m2, eGFRs <5 and ≥12mL/min/1.73m2 were associated with lower and higher mortality, with adjusted HRs of 0.57 (95% CI, 0.43-0.74) and 1.31 (95% CI, 1.05-1.65), respectively. In age-stratified analysis, there were consistent relationships among patients 6 years and older while the eGFR-mortality association was attenuated among patients younger than 6 years (Pinteraction = 0.002). Possible errors in eGFRs due to methods for serum creatinine measurement. Unmeasured confounders related to eGFR at dialysis therapy initiation. Higher eGFR at dialysis therapy initiation was associated with higher mortality risk. Further studies of eGFR at initiation are needed in pediatric dialysis patients, especially among those younger than 6 years.

Okuda Y ，Soohoo M ，Tang Y ，Obi Y ，Laster M ，Rhee CM ，Streja E ，Kalantar-Zadeh K ... -  《-》