Search

Loss of muscle mass and sarcopenia are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD), and sarcopenia can worsen insidiously in patients with advancing CKD. The temporal dynamics of sarcopenia in patients with progressive loss of kidney function, and its association with future outcomes, is unclear.

There is increasing interest in the therapeutic potential of manipulating the gut microbiome of patients with chronic kidney disease (CKD). This is because there is a substantial deviation from a balanced gut microbiota profile in CKD, with many deleterious downstream effects. Nutritional interventions such as plant-based diets with reduced animal protein intake and the use of probiotics, prebiotics, and synbiotics may alter the microbiome. This article aims to briefly describe what is known about the gut microbiome in patients with CKD, factors contributing to gut dysbiosis, and outline important evidence gaps. Future potential therapies, including restoring the microbiota with food and microbiota-based and metabolomic-based therapies, are also discussed.

Potassium disorders are one of the most common electrolyte abnormalities in patients with chronic kidney disease (CKD), contributing to poor clinical outcomes. Maintaining serum potassium levels within the physiologically normal range is critically important in these patients. Dietary potassium restriction has long been considered a core strategy for the management of chronic hyperkalemia in patients with CKD. However, this has been challenged by recent evidence suggesting a paradigm shift toward fostering more liberalized, plant-based dietary patterns. The advent of novel potassium binders and an improved understanding of gastrointestinal processes involved in potassium homeostasis (e.g., gastrointestinal potassium wasting) may facilitate a paradigm shift and incorporation of heart-healthy potassium-enriched food sources. Nevertheless, uncertainty regarding the risk-benefit of plant-based diets in the context of potassium management in CKD remains, requiring well-designed clinical trials to determine the efficacy of dietary potassium manipulation toward improvement of clinical outcomes in patients with CKD.

Despite over 30 years of evidence for improvements in physical function, physical fitness, and health-related quality of life with exercise training in individuals with chronic kidney disease, access to dedicated exercise training programs remains outside the realm of standard of care for most kidney care programs. In this review, we explore possible reasons for this by comparing approaches in other chronic diseases where exercise rehabilitation has become the standard of care, identifying enablers and factors that need to be addressed for continued growth in this area, and discussing knowledge gaps for future research. For exercise rehabilitation to be relevant to all stakeholders and become a sustainable component of kidney care, a focus on the effect of exercise on clinically relevant outcomes that are prioritized by individuals living with kidney disease, use of evidence-based implementation strategies for diverse settings and populations, and approaching exercise as a medical therapy are required.

We examined the real-world comparative safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. other newer anti-glycemic medications (dipeptidyl peptidase-4 inhibitors [DPP4i], glucagon-like peptide-1 receptor agonists [GLP1a]) in patients with and without chronic kidney disease (CKD).

Constipation is highly prevalent in advanced chronic kidney disease (CKD), due in part to dietary (e.g., fiber) restrictions, and is often managed by laxatives; however, the effect of laxative use on kidney function in advanced CKD remains unclear. We aimed to examine the association of laxative use with longitudinal change in estimated glomerular filtration rate (eGFR) in patients with advanced CKD.

Introduction:Patients with advanced non-dialysis-dependent CKD (NDD-CKD) have a reduced ability for maintaining plasma potassium (K) in normal range. Deviation from normal plasma Kranges is associated with increased mortality; however, the average trajectory of plasma Kover time in patients with advanced NDD-CKD and the outcomes associated with plasma Ktrajectory are unknown. Methods:We identified 34,167 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 and March 2015 with at least 1 Kmeasurement each year over a 3-year period prior to dialysis transition (3-year prelude). The Ktrajectory defined as the change in K(slope) per year over the entire 3-year prelude was estimated using linear mixed-effects models. The association between unadjusted (crude) Kslope (categorized as stable [−0.09 to 0.09 mEq/L/year], decreasing [≤−0.10 mEq/L/year], and increasing [≥0.10 mEq/L/year]) and time to all-cause and cardiovascular mortality during the 6 months following dialysis initiation was assessed using multivariable-adjusted survival models. Results:The crude and multivariable-adjusted Kslopes (mean, 95% CI) over the 3-year prelude were 0.008 (0.0059, 0.0110) and −0.15 mEq/L/year (−0.19, −0.11), respectively. Decreasing Kslope was associated with higher multivariable-adjusted risk of all-cause mortality (adjusted hazard ratio [95% CI] vs. stable Kslope: 1.08 [1.00–1.17]). No association was observed between Kslope and cardiovascular mortality. Discussion/Conclusion:The average intraindividual plasma Ktrajectory is remarkably stable in patients with advanced NDD-CKD. A decreasing Kslope is associated with higher all-cause mortality risk.

The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis.

Introduction and Objective:The impact of pretransplant donor-specific antibodies (DSAs), especially class II DSAs, on kidney allograft outcomes remains unclear in simultaneous liver-kidney transplantation (SLKT) recipients. Methods:We examined 85 recipients who consecutively underwent SLKT between 2009 and 2018 in our center. Associations between pretransplant DSA and worsening kidney function (WKF), kidney allograft loss, composite kidney outcome (WKF and/or antibody-mediated rejection and/or death-censored kidney allograft loss), death with functioning graft, and overall mortality were examined in survival analysis. WKF was defined as an eGFR decrease of 30% or greater from baseline, or 2 or more episodes of proteinuria, at least 90 days apart from each other. Results:The mean age at SLKT was 56 ± 10 years, and 62% of the recipients were male. More than one quarter (26%) of our recipients were African American. The 2 major causes of end-stage liver disease were hepatitis C (28%) and alcoholic hepatitis (26%). Nineteen recipients (22%) had pretransplant DSAs at the time of SLKT. The DSA(+) group and DSA(−) group had similar risk of WKF (unadjusted model: hazard ratio [HR] = 0.77, 95% confidence interval [CI]: 0.29–2.05 and adjusted model: HR = 0.36, 95% CI: 0.12–1.08); similar risk of composite kidney outcome (unadjusted model: HR = 1.04, 95% CI: 0.45–2.43 and adjusted model: HR = 0.53, 95% CI: 0.20–1.39); and similar risk of overall death (unadjusted model: HR = 1.23, 95% CI: 0.45–3.36 and adjusted model: HR = 1.28, 95% CI: 0.42–3.87). We found similar results when comparing different DSA subclasses (class I and II DSAs) with recipients without DSAs. Conclusions:The presence of pretransplant DSAs was not associated with worse kidney allograft outcomes from our single-center experience. Further prospective larger studies are strongly warranted.

ABSTRACTPatients with end-stage kidney disease (ESKD) display features of premature aging. There is strong evidence that changes in DNA methylation (DNAm) contribute to age-related pathologies; however, little is known about their association with premature aging and cardiovascular mortality in patients with ESKD. We assayed genome-wide DNAm in a pilot case-control study of 60 hemodialysis patients with (n=30, cases) and without (n=30, controls) a fatal cardiovascular event. DNAm was profiled on the Illumina EPIC BeadChip. Four established DNAm clocks (i.e., Horvath-, Hannum-, Pheno-, and GrimAge) were used to estimate epigenetic age (DNAmAge). Epigenetic age acceleration (EAA) was derived as the residuals of regressing DNAmAge on chronological age (chroAge), and its association with cardiovascular death was examined using multivariable conditional logistic regression. An epigenome-wide association study (EWAS) was performed to identify differentially methylated CpGs associated with cardiovascular death. All clocks performed well at predicting chroAge (correlation between DNAmAges and chroAge of r=0.76-0.89), with GrimAge showing the largest deviation from chroAge (a mean of +21.3 years). There was no significant association of EAAs with cardiovascular death. In the EWAS, a CpG (cg22305782) in the FBXL19gene had the strongest association with cardiovascular death with significantly lower DNAm in cases vs. controls (PFDR=2.0x10−6). FBXL19is involved in cell apoptosis, inflammation, and adipogenesis. Overall, we observed more accelerated aging in patients with ESKD, although there was no significant association of EAAs with cardiovascular death. EWAS suggests a potential novel DNAm biomarker for premature cardiovascular mortality in ESKD.

Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies.

Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.

Background:Cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often difficult to treat. However, the factors influencing cyst infection are still unknown. Therefore, we investigated clinical factors related to the duration of hospitalization and death due to cyst infection. Methods:All ADPKD patients undergoing cyst drainage or nephrectomy or partial hepatectomy at Toranomon Hospital from January 2004 to March 2016, in whom cyst fluid analysis showed bacteria or neutrophils indicating definite cyst infection, were reviewed retrospectively. Factors influencing the duration of hospitalization and death due to cyst infection were analyzed. Results:A total of 243 patients with cyst infection were enrolled, including 104 men and 139 women (mean age: 62.6 ± 10.0 years). Seventeen patients died of cyst infection. Multivariate logistic regression analysis revealed that hepatomegaly, positive cyst contents culture, and the maximum white blood cell (WBC) count were significantly associated with death from cyst infection. Death was significantly more likely if patients had massive hepatomegaly (≥5,113.2 mL) compared with mild hepatomegaly (< 1,898.7 mL; odds ratio 38.1; 95% CI 2.9–492.6, p= 0.0004). Multivariate Cox proportional hazards analysis revealed that older age, dialysis duration, hepatic transcatheter arterial embolization, maximum WBC count, and hepatomegaly were significantly associated with longer hospital stay for cyst infection, while female sex, nephrectomy, serum albumin, and serum cholinesterase were significantly associated with shorter hospital stay. Discharge alive from hospital was significantly associated with massive hepatomegaly versus mild hepatomegaly (hazard ratio 0.0072; 95% CI 0.0008–0.0659, p< 0.0001). Conclusions:Hepatomegaly was strongly associated with both death and longer hospital stay due to cyst infection.

A recent study demonstrated that tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in later-stage autosomal dominant polycystic kidney disease (ADPKD) patients. However, Japanese patients were not included in that trial, therefore tolvaptan’s efficacy in Japanese patients with advanced chronic kidney disease (CKD) has remained unknown. In this prospective cohort study, 54 patients with ADPKD who had eGFR ≥ 15 ml/min/1.73 m2and total kidney volume (TKV) ≥ 750 ml were treated with tolvaptan. The primary endpoint was the change in height-adjusted total kidney volume (htTKV) and eGFR after 1-year treatment with tolvaptan. Then, we compared the primary endpoint between later CKD stage (baseline eGFR < 45 ml/min/1.73 m2) and earlier CKD stage (baseline eGFR ≥ 45 ml/min/1.73 m2). The rate of kidney growth during the 1-year treatment did not differ significantly between earlier and later CKD stages. The median and interquartile range of relative change in htTKV in later CKD stage was 8.2%/year [4.4, 26.6], as compared with 5.7%/year [1.6, 16.4] in earlier CKD stage (p = 0.17). Nor did the rate of eGFR decline between earlier and later CKD stages. The relative annual change in eGFR in later CKD stage was − 9.7%/year [− 15.9, − 2.1], as compared with − 6.8%/year [− 11.1, 0.1] in earlier CKD stage (p = 0.18). This analysis indicates that the efficacy of tolvaptan for Japanese patients with later stage ADPKD was not significantly different from that of Japanese patients with earlier stage ADPKD.

To determine whether kidney function level and its rate of decline in the immediate predialysis period among veterans transitioning to end-stage renal disease (ESRD) predict postdialysis mortality and hospitalization.

Rheumatoid arthritis is associated with reduced kidney function, possibly due to chronic inflammation or the use of nephrotoxic therapies. However, little is known about the effects of using the newer novel non-nephrotoxic biologic agents on the risk of incident chronic kidney disease (CKD). To study this we used a cohort of 20,757 United States veterans diagnosed with rheumatoid arthritis with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2or more, recruited between October 2004 and September 2006, and followed through 2013. The associations of biologic use with incident CKD (eGFR under 60 with a decrease of at least 25% from baseline, and eGFR under 45 mL/min/1.73m2) and change in eGFR (<-3, -3 to <0 [reference], and ≥0 mL/min/1.73m2/year) were examined in propensity-matched patients based on their likelihood to initiate biologic treatment, using Cox models and multinomial logistic regression models, respectively. Among 20,757 patients, 4,617 started biologic therapy. In the propensity-matched cohort, patients treated (versus not treated) with biologic agents had a lower risk of incident CKD (hazard ratios 0.95, 95% confidence interval [0.82-1.10] and 0.71 [0.53-0.94] for decrease in eGFR under 60 and under 45 mL/min/1.73m2, respectively) and progressive eGFR decline (multinomial odds ratios [95% CI] for eGFR slopes <-3 and ≥0 [versus -3 to <0] mL/min/1.73m2/year, 0.67 [0.58-0.79] and 0.76 [0.69-0.83], respectively). A significant deceleration of eGFR decline was also observed after biologic administration in patients treated with biologics (-1.0 versus -0.4 [mL/min/1.73m2/year] before and after biologic use). Thus, biologic agent administration was independently associated with lower risk of incident CKD and progressive eGFR decline.

Reduced lung function is associated with clinical outcomes such as cardiovascular disease. However, little is known about its association with incident end-stage renal disease (ESRD) and chronic kidney disease (CKD).

Background/Aims:All hemodialysis (HD) patients are generally recommended to create a fistula first; but to create a mature arteriovenous fistula (AVF) can be challenging in elderly individuals. It is unclear if elderly incident HD patients derive a survival benefit from an AVF over an arteriovenous graft (AVG) or a tunneled central venous catheter (TDC). Methods:We examined the association of vascular access type (AVF, AVG, and TDC with and without a maturing AVF/AVG at dialysis transition) at HD initiation with all-cause, cardiovascular (CV), and infection-related mortality in 46,786 US veterans using Cox models with adjustment for confounders. Effect modification by age was examined by examining associations in pre-specified age subgroups (<60, 60-<70, 70-<80, and ≥80 years old), and by including interaction terms. Results:Patients numbering 8,940 (19%) started HD with an AVF, 1,090 (3%) with an AVG, 8,262 (18%) with a TDC and a maturing AVF/AVG and 28,494 (61%) with a TDC without a maturing AVF/AVG. A total of 13,303 all-cause, 4,392 CV, and 1,058 infection-related deaths were observed in the first year after HD transition. Compared to patients with AVF, those with AVG and TDC with and without maturing AVF/AVG had incrementally higher overall risk of all-cause mortality and CV mortality. Only TDC use was associated with higher infection-associated mortality. These associations were not modified by age. Conclusion:Although most of our patients consisted of male veterans and the results may not be generalized to the general population, the use of TDCs is associated with poor outcomes even in the most elderly incident HD patients.

Supplemental Digital Content is available in the text

Background:Mortality in the immediate post-hemodialysis transition period is extremely high. Many end-stage renal disease (ESRD) patients in the US start dialysis in an inpatient setting, but the characteristics of patients starting dialysis as inpatients, and the association of inpatient hemodialysis transition with mortality remain unclear. Methods:We examined 48,261 US veterans who transitioned to hemodialysis between October 2007 and September 2011. Associations of inpatient hemodialysis starting with all-cause mortality were examined in Cox proportional hazard models, with adjustments for demographics, comorbidities, vascular access type, pre-dialysis nephrology care and medication use, and last pre-ESRD estimated glomerular filtration rate and hemoglobin. Results:A total of 22,338 (46.3%) patients received the first hemodialysis treatment in an inpatient setting. Inpatient hemodialysis transition was associated with older age, presence of a tunneled catheter, higher comorbidity burden, and lack of pre-dialysis nephrology care. A total of 8,674 patients died (mortality rate 405/1,000 patient-years, 95% CI 397-413) during the first 6 months after transition to hemodialysis. The starting of inpatient vs. outpatient hemodialysis was associated with significantly higher crude all-cause mortality, but this association was attenuated after multivariable adjustments. Conclusions:Transition to hemodialysis in an inpatient setting is more common in older and sicker individuals, and in patients without pre-dialysis nephrology care and those who used a catheter for vascular access. Future studies are needed to determine if a higher proportion of patients could start hemodialysis treatment in outpatient clinics, through interventions targeting modifiable risk factors such as timely vascular access placement or earlier nephrology referrals.

Mortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after dialysis therapy initiation remains unknown.

One of the biggest challenges nephrologists face is to predict complex clinical pathways of kidney disease progression that do not follow a steady linear decline. This unpredictability often becomes a barrier to timely shared decision making between patients and physicians and could lead to adverse patient outcomes. By using numerous analytic approaches to characterize the longitudinal changes in kidney function, emerging evidence has disclosed the heterogeneous trajectories of kidney disease progression, particularly in late-stage chronic kidney disease (CKD) nearing end-stage renal disease (ESRD), and showed their independent associations with various clinical outcomes. These findings, in turn, have reinforced the importance of incorporating individual kidney disease trajectories into the clinical management of patients with late-stage CKD, which may help clarify the optimal timing of preparatory interventions, such as vascular access planning and transplant referral, and deliver better care with potential downstream benefits, such as a lower incidence of ESRD or a more seamless transition to ESRD. In this article, we review the current evidence on trajectories of kidney disease progression, particularly among patients with late-stage CKD progressing to ESRD, and discuss their implications for clinical management.

Summary:Recent advances in microbiome research have informed the potential role of the gut microbiota in the regulation of metabolic, cardiovascular, and renal systems, and, when altered, in the pathogenesis of various cardiometabolic disorders, including chronic kidney disease (CKD). The improved understanding of gut dysbiosis in cardiometabolic pathologies in turn has led to a vigorous quest for developing therapeutic strategies. These therapeutic strategies aim to investigate whether interventions targeting gut dysbiosis can shift the microbiota toward eubiosis and if these shifts, in turn, translate into improvements in (or prevention of) CKD and its related complications, such as premature cardiovascular disease. Existing evidence suggests that multiple interventions (eg, plant-based diets; prebiotic, probiotic, and synbiotic supplementation; constipation treatment; fecal microbiota transplantation; and intestinal dialysis) might result in favorable modulation of the gut microbiota in patients with CKD, and thereby potentially contribute to improving clinical outcomes in these patients. In this review, we summarize the current understanding of the characteristics and roles of the gut microbiota in CKD and discuss the potential of emerging gut microbiota–targeted interventions in the management of CKD.

Nutrition is an integral component in the management of chronic kidney disease (CKD), and kidney health professionals play a crucial role in educating patients on dietary interventions for CKD. Several dietary modifications are indicated for CKD that require frequent adaptations with CKD progression and with underlying metabolic disturbances. However, poor adherence to dietary interventions is not uncommon among patients with CKD. An effective education program on nutrition intervention consists of providing knowledge and developing skills that are necessary to support behavioral change. The application of theoretical models of behavioral change such as social cognitive theory and the transtheoretical model in nutrition intervention has been reported to be effective in promoting changes in dietary habits. This review summarizes the evidence supporting the application of theoretical models as strategies to enhance nutrition education for patients with CKD. In addition, digital technologies are gaining interest in empowering patients and facilitating nutrition management in patients with CKD. This review also examines the applications of the latest digital technologies guided by behavioral theory in facilitating patients’ changes in dietary intake patterns and lifestyle habits.

Context:Abnormalities in calcium metabolism may potentially contribute to the development of vascular disease. Calcium metabolism may be different in African American (AA) vs white individuals, but the effect of race on the association of serum calcium with clinical outcomes remains unclear.Objective:This study sought to examine race-specific associations of serum calcium levels with mortality and with major incident cardiovascular events.Design and Setting:This was a historical cohort study in the U.S. Department of Veterans Affairs health care facilities.Participants:Participants included veterans (n = 1 967 622) with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2.Main Outcome Measures:The association between serum calcium levels with all-cause mortality, incident coronary heart disease (CHD), and ischemic stroke incidence was examined in multivariable adjusted Cox proportional hazards models, including an interaction term for calcium and race.Results:The association of calcium with all-cause mortality was U-shaped in both AA and white patients, but race modified the association of calcium with all-cause mortality. Compared with white patients, AA patients experienced lower risk of mortality when calcium was ≥ 8.8 mg/dL, with a statistically significant interaction (P< .001). Conversely, AA vs white race was associated with higher mortality when calcium was < 8.8 mg/dL. Calcium showed no significant association with ischemic stroke or CHD in both races; and race did not modify these associations (P= .37 and 0.11, respectively for interaction term).Conclusions:Race modified the U-shaped association between calcium and all-cause mortality. Serum calcium is not associated with incident stroke or CHD in either AA or white patients. The race-specific difference in the association of calcium levels with mortality warrants further examination.

Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among patients with advanced chronic kidney disease and mortality following their transition to dialysis.

Supplemental Digital Content is available in the text

While dialysis has been the prevailing treatment paradigm for patients with advanced chronic kidney disease (CKD), emphasis on conservative and preservative management in which dietary interventions are a major cornerstone have emerged. Based on high-quality evidence, international guidelines support the utilization of low-protein diets as an intervention to reduce CKD progression and mortality risk, although the precise thresholds (if any) for dietary protein intake vary across recommendations. There is also increasing evidence demonstrating that plant-dominant low-protein diets reduce the risk of developing incident CKD, CKD progression, and its related complications including cardiometabolic disease, metabolic acidosis, mineral and bone disorders, and uremic toxin generation. In this review, we discuss the premise for conservative and preservative dietary interventions, specific dietary approaches used in conservative and preservative care, potential benefits of a plant-dominant low-protein diet, and practical implementation of these nutritional strategies without dialysis.