Reconciling diagnostic definitions for proposing metabolic dysfunction-associated steatotic liver disease in chronic kidney disease risk

Published literature suggests that sleep duration and quality may be affected in adults with chronic kidney disease. However, the relationship between these two entities remains a matter of debate. The objective of this systematic review and meta-analysis is to assess the effect of sleep duration and quality on chronic kidney disease. A systematic review of the Medline/PubMed, Embase, Cochrane Library, and CINAHL databases was conducted for articles pertaining to the association between sleep duration and quality on chronic kidney disease. The main outcome was the hazard/risk ratio of chronic kidney disease in patients of varying sleep durations and quality. In total, 42 studies (2613971 patients) with a mean age of 43.55±14.01 years were included in the meta-analysis. Compared with a reference range of 7 to 8 hours of sleep, short sleep durations of ≤4 hours (RR 1.41, 95% CI: 1.16 to 1.71, P<0.01), ≤5 hours (RR 1.46, 95% CI: 1.22 to 1.76, P<0.01), ≤6 hours (RR 1.18, 95% CI: 1.09 to 1.29, P<0.01), and ≤7 hours (RR 1.19, 95% CI: 1.12 to 1.28, P<0.01) were significantly associated with an increased risk of incident chronic kidney disease. Long sleep durations of ≥8 hours (RR 1.15, 95% CI: 1.03 to 1.28, P<0.01) and ≥9 hours (RR 1.46, 95% CI: 1.28 to 1.68, P<0.01) were also significantly associated with an increased risk of incident chronic kidney disease. Meta-regression did not find any significant effect of age, gender, geographical region, and BMI and an association with sleep duration and risk of incident chronic kidney disease. Both short and long sleep durations were significantly associated with a higher risk of chronic kidney disease. Interventions targeted toward achieving an optimal duration of sleep may reduce the risk of incident chronic kidney disease.

BackgroundWe examined the comparative associations between non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) definitions with risk of developing chronic kidney disease (CKD) and abnormal albuminuria.MethodsWe conducted a cohort study of 214,145 Korean adults with normal kidney function at baseline who underwent liver ultrasonography. Participants were further subdivided into no steatotic liver disease (no-SLD), NAFLD-only, MASLD-only, both NAFLD and MASLD, and SLD not categorized as NAFLD or MASLD groups. Cox proportional hazards models were used to analyze the risk of incident CKD and albuminuria.ResultsCompared with either the no-NAFLD or no-MASLD groups, the NAFLD and MASLD groups were associated with a higher risk of incident CKD (NAFLD: adjusted hazard ratio (HR), 1.18 [95% CI, 1.01-1.38]; MASLD: adjusted HR, 1.21 [95% CI, 1.04-1.39]). Among the five subgroups, both NAFLD and MASLD group had the strongest association with risk of incident CKD (adjusted HR, 1.21 [95% CI, 1.04-1.42]). The MASLD-only group had the strongest association with incident abnormal albuminuria, with an adjusted HR comparable to that of the both NAFLD and MASLD group (adjusted HR 1.96 [95% CI, 1.44-2.67] for the MASLD-only, and adjusted HR 1.98 [95% CI, 1.58-2.49] for the both NAFLD and MASLD group versus the no-SLD group). The NAFLD-only group was not independently associated with risk of CKD or abnormal albuminuria.ConclusionsThese findings suggest that MASLD definition identifies individuals at high risk of developing incident CKD or abnormal albuminuria better than NAFLD definition.

Does Inflammation Fuel the Fire in CKD?

With the rising tide of fatty liver disease related to metabolic dysfunction worldwide, the association of this common liver disease with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the old term non-alcoholic fatty liver disease (NAFLD). In 2023, a modified Delphi process was led by three large pan-national liver associations. There was consensus to change the fatty liver disease nomenclature and definition to include the presence of at least one of five common cardiometabolic risk factors as diagnostic criteria. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). The change of nomenclature from NAFLD to MAFLD and then MASLD has resulted in a reappraisal of the epidemiological trends and associations with the risk of developing CKD. The observed association between MAFLD/MASLD and CKD and our understanding that CKD can be an epiphenomenon linked to underlying metabolic dysfunction support the notion that individuals with MASLD are at substantially higher risk of incident CKD than those without MASLD. This narrative review provides an overview of the literature on (a) the evolution of criteria for diagnosing this highly prevalent metabolic liver disease, (b) the epidemiological evidence linking MASLD to the risk of CKD, (c) the underlying mechanisms by which MASLD (and factors strongly linked with MASLD) may increase the risk of developing CKD, and (d) the potential drug treatments that may benefit both MASLD and CKD.

BackgroundStillbirth is a devastating adverse pregnancy outcome that may occur without any obvious reason or may occur in the context of fetal growth restriction, preeclampsia, or other obstetric complications. There is increasing evidence that women who experience stillbirths are at greater risk of long-term cardiovascular disease, but little is known about their risk of chronic kidney disease and end-stage renal disease. We conducted the largest study to date to investigate the subsequent risk of maternal chronic kidney disease and end-stage renal disease following stillbirth.ObjectiveTo identify whether pregnancy complicated by stillbirth is associated with subsequent risk of maternal chronic kidney disease and end-stage renal disease, independent of underlying medical or obstetric comorbidities.Study Design/MethodsWe conducted a population-based cohort study using nationwide data from the Swedish Medical Birth Register, National Patient Register, and Swedish Renal Register. We included all women who had live births and stillbirths from 1973 to 2012, with follow-up to 2013. Women with preexisting renal disease were excluded. Cox proportional hazard regression models were used to estimate adjusted hazard ratios and 95% confidence intervals for associations between stillbirth and maternal chronic kidney disease and end-stage renal disease respectively. We controlled for maternal age, year of delivery, country of origin, parity, body mass index, smoking, gestational diabetes, preeclampsia, and small for gestational age deliveries. Women who had a history of medical comorbidities, which may predispose to renal disease (prepregnancy cardiovascular disease, hypertension, diabetes, lupus, systemic sclerosis, hemoglobinopathy, or coagulopathy), were excluded from the main analysis and examined separately.ResultsThere were 1,941,057 unique women who had 3,755,444 singleton pregnancies, followed up over 42,313,758 person-years. The median follow-up time was 20.7 years (interquartile range, 9.9–30.0 years). 13,032 women (0.7%) had at least 1 stillbirth. Women who had experienced at least 1 stillbirth had a greater risk of developing chronic kidney disease (adjusted hazard ratio, 1.26; 95% confidence interval, 1.09–1.45) and end-stage renal disease (adjusted hazard ratio, 2.25; 95% confidence interval, 1.55–3.25) compared with women who only had live births. These associations persisted after removing all stillbirths that occurred in the context of preeclampsia, and small for gestational age or congenital malformations (for chronic kidney disease, adjusted hazard ratio, 1.33; 95% confidence interval, 1.13–1.57; for end-stage renal disease, adjusted hazard ratio, 2.95; 95% confidence interval, CI 1.86–4.68). There was no significant association observed between stillbirth and either chronic kidney disease or end-stage renal disease in women who had preexisting medical comorbidities (chronic kidney disease, adjusted hazard ratio, 1.13; 95% confidence interval, 0.73–1.75 or end-stage renal disease, adjusted hazard ratio, 1.49; 95% confidence interval, 0.78–2.85).ConclusionWomen who have a history of stillbirth may be at increased risk of chronic kidney disease and end-stage renal disease compared with women who have only had live births. This association persists independently of preeclampsia, and small for gestational age, maternal smoking, obesity, and medical comorbidities. Further research is required to determine whether affected women would benefit from closer surveillance and follow-up for future renal disease.

The association between abdominal visceral adipose tissue and the risk of incident chronic kidney disease according to body mass index in the Asian population, remains unclear. We evaluated the impact of abdominal adiposity stratified by body mass index on the risk of incident chronic kidney disease. A cohort study included 11,050 adult participants who underwent health check-ups and re-evaluated the follow-up medical examination at a single university-affiliated healthcare center. Cross-sectional abdominal adipose tissue areas were measured using computed tomography. The primary outcome was progression to chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2). The highest quartile of visceral adipose tissue was used for the cut-off of central obesity. During the mean of 5.6 follow-up years, 104 incident chronic kidney disease cases were identified. The risk for chronic kidney disease incidence was significantly increased in the 3rd and 4th quartile ranges of visceral adipose tissue [hazard ratio (95% confidence interval)]: 4.59 (1.48-14.30) and 7.50 (2.33-24.20), respectively. In the analysis stratified by body mass index, the chronic kidney disease incidence risk was increased in the highest quartile range of visceral adipose tissue in the normal weight group: 7.06 (1.35-37.04). However, there was no significant relationship between visceral adipose tissue and chronic kidney disease in the obese group. Compared to the subjects with normal weight and absent central obesity, the hazard ratio for chronic kidney disease incidence was 2.32 (1.26-4.27) among subjects with normal weight and central obesity and 1.81 (1.03-3.15) among subjects with obesity and central obesity. Visceral adipose tissue was a significant risk factor for subsequent chronic kidney disease progression, and the association was identified only in the normal weight group. Normal-weight central obesity was associated with excess risk of chronic kidney disease, similar to the risk in the group with obesity and central obesity.

Primary Versus Secondary Prevention of Chronic Kidney Disease: The Case of Dietary Protein

Accumulating evidence now indicates that non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease observed in clinical practice worldwide, is independently associated with an increased risk of incident chronic kidney disease (CKD). Given that NAFLD is linked to insulin resistance, obesity and type 2 diabetes mellitus, an international panel of experts have recently proposed a name change from NAFLD to metabolic associated fatty liver disease (MAFLD). Since the diagnostic criteria for NAFLD and MAFLD are different, observational studies assessing the potential concordance (or even superiority) of MAFLD, compared with NAFLD, in detecting patients at increased risk of hepatic and extra-hepatic complications (including CKD) are required. Hence, in the last two years, some observational studies have investigated the potential relationship between MAFLD and CKD. The result is that, at present, evidence regarding the concordance or even superiority of MAFLD, compared with NAFLD, in detecting patients at higher risk of CKD is still preliminary, although some data indicate that MAFLD identifies patients with CKD as accurately as NAFLD. In this narrative review, we will discuss: (a) the epidemiological evidence assessing the association between NAFLD and risk of incident CKD, (b) the epidemiological data investigating the association between MAFLD and risk of CKD and (c) the biological mechanisms underlying the association between NAFLD/MAFLD and CKD.

BackgroundSocioeconomic status (SES) and cardiorespiratory fitness (CRF) are each independently associated with chronic kidney disease. The interplay among SES, CRF, and chronic kidney disease is not well understood. We aimed to evaluate the separate and joint associations of SES and CRF with chronic kidney disease risk in a cohort of Caucasian men. MethodsIn 2099 men aged 42-61 years with normal kidney function at baseline, SES was self-reported and CRF was directly measured using a respiratory gas exchange analyzer during cardiopulmonary exercise testing. Hazard ratios (HRs) (95% confidence interval) were estimated for chronic kidney disease. ResultsA total of 197 chronic kidney disease events occurred during a median follow-up of 25.8 years. Comparing low versus high SES, the multivariable-adjusted HR (95% confidence interval) for chronic kidney disease was 1.55 (1.06-2.25), which remained consistent on further adjustment for CRF 1.53 (1.06-2.22). Comparing high versus low CRF, the multivariable-adjusted HR for chronic kidney disease was 0.66 (0.45-0.96), which persisted on further adjustment for SES 0.67 (0.46-0.97). Compared with high SES-high CRF, low SES-low CRF was associated with an increased risk of chronic kidney disease 1.88 (1.23-2.87), with no evidence of an association for low SES-high CRF and chronic kidney disease risk 1.32 (0.85-2.05). Positive additive (relative excess risk due to interaction = 0.31) and multiplicative (ratio of HRs = 1.14) interactions were found between SES and CRF in relation to chronic kidney disease risk. ConclusionsIn middle-aged and older males, SES and CRF are each independently associated with risk of incident chronic kidney disease. There exists an interplay among SES, CRF and chronic kidney disease risk, with high CRF levels appearing to offset the increased chronic kidney disease risk related to low SES.

The effect of dyslipidemia on kidney disease outcomes has been inconclusive, and it requires further clarification. Therefore, we aimed to investigate the effects of genetic factors on the association between dyslipidemia and the risk of chronic kidney disease (CKD) using polygenic risk score (PRS). We analyzed data from 373,523 participants from the UK Biobank aged 40-69 years with no history of CKD. Baseline data included plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride, as well as genome-wide genotype data for PRS. Our primary outcome, incident CKD, was defined as a composite of estimated glomerular filtration rate < 60 ml/min/1.73 m2 and CKD diagnosis according to International Classification of Disease-10 codes. The effects of the association between lipid levels and PRS on incident CKD were assessed using the Cox proportional hazards model. To investigate the effect of this association, we introduced multiplicative interaction terms into a multivariate analysis model and performed subgroup analysis stratified by PRS tertiles. In total, 4,424 participants developed CKD. In the multivariable analysis, PRS was significantly predictive of the risk of incident CKD as both a continuous variable and a categorized variable. In addition, lower total cholesterol, LDL-C, HDL-C, and higher triglyceride levels were significantly associated with the risk of incident CKD. There were interactions between triglycerides and intermediate and high PRS, and the interactions were inversely associated with the risk of incident CKD. This study showed that PRS presented significant predictive power for incident CKD and individuals in the low-PRS group had a higher risk of triglyceride-related incident CKD.

Nutrition and Kidney Health: Processing Emerging Evidence About Foods

Metabolic dysfunction-associated fatty liver disease can significantly increase the risk of chronic kidney disease in adults with type 2 diabetes

Background It is unclear whether individuals with Down syndrome (DS) are at increased risk of kidney disease. This study aims to examine the risk of acute kidney injury (AKI) and chronic kidney disease (CKD) in individuals with DS compared to the general population. Methods Using the Danish Cytogenetic Central Registry, we identified a population-based cohort of individuals with genetically confirmed DS in Denmark between 1961 and 2021. For each individual with DS, we sampled 10 age-and-sex-matched individuals without DS from the general Danish population. We used laboratory data on plasma creatinine from the 1990s until 2024 to assess AKI and CKD and computed the cumulative incidence (risk) of AKI and CKD by age. Furthermore, we estimated the risk of AKI and CKD in individuals without congenital heart disease (CHD). Results We identified 2,815 individuals with DS and available laboratory data on plasma creatinine measurements. Comparing individuals with DS to the matched cohort, the risk of AKI was 28.9% vs. 1.4% at age 20, 32.8% vs. 5.3% at age 40, and 48.6% vs. 23.8% at age 70. The risk of CKD was 1.2% vs. 0.1% at age 20, 3.9% vs. 0.4% at age 40, and 23.2% vs. 13.8% at age 70. For individuals without CHD, the risk of AKI and CKD remained considerably higher for individuals with DS than for matched individuals. Conclusions Individuals with DS were at increased risk of both AKI and CKD compared to the general population. Kidney disease should be considered during clinical follow-up of DS.

Although type 2 diabetes mellitus (T2DM) plays a significant role in the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD), how T2DM development and glycemic deterioration affect CKD and its renal function indicators, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), remains unknown. We aimed to assess the association between MAFLD, along with T2DM, and risk of CKD, and then evaluate the effect of metabolic goal achievement in MAFLD on the risk of CKD. In this cross-sectional study, 5,594 participants were included. Multivariate logistic regression and linear regression were used to examine the association between MAFLD with its T2DM status and metabolic goal achievement and risk of CKD, as well as eGFR and UACR. The MAFLD group had a higher prevalence of CKD (16.2 vs. 7.6%, P < 0.001) than the non-MAFLD group. MAFLD was independently associated with an increased risk of CKD (odds ratio [OR]: 1.35, 95% CI: 1.09-1.67) and increased eGFR and UACR. Among the three MAFLD subtypes, only the T2DM subtype exhibited significant associations with increased risk of CKD (OR: 2.85, 95% CI: 2.24-3.63), as well as increased eGFR and UACR. Glycemic deterioration in MAFLD was dose-dependently associated with an increased risk of CKD (P-trend < 0.001). Achieved metabolic goals in MAFLD decreased the risk of CKD, eGFR, and UACR; MAFLD with 2 or 3 achieved metabolic goals was not significantly associated with the risk of CKD (OR: 0.81, 95% CI: 0.59-1.12) and albuminuria. MAFLD was independently associated with an increased risk of CKD, as well as increased eGFR and UACR. This association is strongly driven by T2DM status. Glycemic deterioration in MAFLD was dose-dependently associated with an increased risk of CKD. Achieved metabolic goals in MAFLD decreased the risk of CKD by reducing the risk of albuminuria.

Do Children With Acute Kidney Injury Require Long-term Evaluation for CKD?