Background
Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA‐associated hyperkalaemia in real‐world settings and the extent of subsequent ...MRA discontinuation are poorly quantified.
Methods and results
Observational study including all Stockholm citizens initiating MRA therapy during 2007–2010. Hyperkalaemias were identified from all potassium (K+) measurements in healthcare. MRA treatment lengths and dosages were obtained from complete collection of pharmacy dispensations. We assessed the 1‐year incidence and clinical hyperkalaemia predictors, and quantified drug prescription changes after an episode of hyperkalaemia. Overall, 13 726 new users of MRA were included, with median age of 73 years, 53% women and median plasma K+ of 3.9 mmol/L. Within a year, 18.5% experienced at least one detected hyperkalaemia (K+ > 5.0 mmol/L), the majority within the first 3 months of therapy. As a comparison, hyperkalaemia was detected in 6.4% of propensity‐matched new beta‐blocker users. Chronic kidney disease (CKD), older age, male sex, heart failure, peripheral vascular disease, diabetes and concomitant use of angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, beta‐blockers and diuretics were associated with increased hyperkalaemia risk. After hyperkalaemia, 47% discontinued MRA and only 10% reduced the prescribed dose. Discontinuation rates were higher after moderate/severe (K+ > 5.5 mmol/L) and early in therapy (<3 months from initiation) hyperkalaemias. CKD participants carried the highest risk of MRA discontinuation in adjusted analyses. When MRA was discontinued, most patients (76%) were not reintroduced to therapy during the subsequent year.
Conclusion
Among real‐world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD.
Abstract Background & Aims Proton pump inhibitors (PPI) have been associated with acute kidney injury (AKI) and recent studies suggest that they may be associated with the risk of chronic kidney ...disease (CKD). Methods We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n= 105305) and new users of H2 blockers (H2B; n= 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury (AKI). Complete collection of repeated PPI and H2B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated to cumulative PPI exposure. Results Users of PPIs, compared to users of H2Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio HR, 1.26; 95% CI, 1.05–1.51) and decrease in estimated glomerular filtration rate of 30% or more (11045 events; 1.26; 95% CI, 1.16–1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 0.76–7.58) and AKI (HR, 1.30; 95% CI, 1.00–1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H2B use. Conclusions Initiation of PPI therapy and cumulative PPI exposure associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.
Background Individuals on dialysis therapy have a high risk for infection, but risk for infection in earlier stages of chronic kidney disease has not been comprehensively described. Study Design ...Observational cohort study. Setting & Participants 9,697 participants (aged 53-75 years) in the Atherosclerosis Risk in Communities (ARIC) Study. Participants were followed up from 1996 to 1998 through 2011. Predictors Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR). Outcomes Risk for hospitalization with infection and death during or within 30 days of hospitalization with infection. Results During follow-up (median, 13.6 years), there were 2,701 incident hospitalizations with infection (incidence rate, 23.6/1,000 person-years) and 523 infection-related deaths. In multivariable analysis, HRs of incident hospitalization with infection as compared to eGFRs ≥ 90 mL/min/1.73 m2 were 2.55 (95% CI, 1.43-4.55), 1.48 (95% CI, 1.28-1.71), and 1.07 (95% CI, 0.98-1.16) for eGFRs of 15 to 29, 30 to 59, and 60 to 89 mL/min/1.73 m2 , respectively. Corresponding HRs were 3.76 (95% CI, 1.48-9.58), 1.62 (95% CI, 1.20-2.19), and 0.99 (95% CI, 0.80-1.21) for infection-related death. Compared to ACRs < 10 mg/g, HRs of incident hospitalization with infection were 2.30 (95% CI, 1.81-2.91), 1.56 (95% CI, 1.36-1.78), and 1.34 (95% CI, 1.20-1.50) for ACRs ≥ 300, 30 to 299, and 10 to 29 mg/g, respectively. Corresponding HRs were 3.44 (95% CI, 2.28-5.19), 1.57 (95% CI, 1.18-2.09), and 1.39 (95% CI, 1.09-1.78) for infection-related death. Results were consistent when separately assessing risk for pneumonia, kidney and urinary tract infections, bloodstream infections, and cellulitis and when taking into account recurrent episodes of infection. Limitations Outcome ascertainment relied on diagnostic codes at time of discharge. Conclusions Increasing provider awareness of chronic kidney disease as a risk factor for infection is needed to reduce infection-related morbidity and mortality.
Traditional dietary recommendations for patients with chronic kidney disease (CKD) focus on the quantity of nutrients consumed. Without appropriate dietary counselling, these restrictions can result ...in a low intake of fruits and vegetables and a lack of diversity in the diet. Plant nutrients and plant-based diets could have beneficial effects in patients with CKD: increased fibre intake shifts the gut microbiota towards reduced production of uraemic toxins; plant fats, particularly olive oil, have anti-atherogenic effects; plant anions might mitigate metabolic acidosis and slow CKD progression; and as plant phosphorus has a lower bioavailability than animal phosphorus, plant-based diets might enable better control of hyperphosphataemia. Current evidence suggests that promoting the adoption of plant-based diets has few risks but potential benefits for the primary prevention of CKD, as well as for delaying progression in patients with CKD G3-5. These diets might also help to manage and prevent some of the symptoms and metabolic complications of CKD. We suggest that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition should be individualized to avoid depriving patients with CKD of these potential beneficial effects of plant-based diets. However, research is needed to address knowledge gaps, particularly regarding the relevance and extent of diet-induced hyperkalaemia in patients undergoing dialysis.
The first reports connecting uremic inflammation with a wasted and atherogenic phenotype and poor outcome initiated in the late 1990s. Since then, about 3500 publications appear on Medline, ...reflecting the exponential interest that this topic has evoked in nephrology. What was described as a “novel” risk factor 10 years ago has now evolved into an established finding in patients with end‐stage renal disease (ESRD). The purpose of this review is to summarize the main advances contributing to our current understanding of the complex inflammatory processes present in ESRD. Causes and consequences of inflammation, genetic heritability of the inflammatory response, implications on outcome prognostication, and contemporary therapeutic evidence are some of the various topics discussed.
It is unknown whether stopping renin-angiotensin system (RAS) inhibitor therapy in patients with advanced CKD affects outcomes.
We studied patients referred to nephrologist care, listed on the ...Swedish Renal Registry during 2007-2017, who developed advanced CKD (eGFR<30 ml/min per 1.73 m
) while on RAS inhibitor therapy. Using target trial emulation techniques on the basis of cloning, censoring, and weighting, we compared the risks of stopping within 6 months and remaining off treatment versus continuing RAS inhibitor therapy. These included risks of subsequent 5-year all-cause mortality, major adverse cardiovascular events, and initiation of kidney replacement therapy (KRT).
Of 10,254 prevalent RAS inhibitor users (median age 72 years, 36% female) with new-onset eGFR <30 ml/min per 1.73 m
, 1553 (15%) stopped RAS inhibitor therapy within 6 months. Median eGFR was 23 ml/min per 1.73 m
. Compared with continuing RAS inhibition, stopping this therapy was associated with a higher absolute 5-year risk of death (40.9% versus 54.5%) and major adverse cardiovascular events (47.6% versus 59.5%), but with a lower risk of KRT (36.1% versus 27.9%); these corresponded to absolute risk differences of 13.6 events per 100 patients, 11.9 events per 100 patients, and -8.3 events per 100 patients, respectively. Results were consistent whether patients stopped RAS inhibition at higher or lower eGFR, across prespecified subgroups, after adjustment and stratification for albuminuria and potassium, and when modeling RAS inhibition as a time-dependent exposure using a marginal structural model.
In this nationwide observational study of people with advanced CKD, stopping RAS inhibition was associated with higher absolute risks of mortality and major adverse cardiovascular events, but also with a lower absolute risk of initiating KRT.
Skeletal muscle mass and muscle function are negatively affected by a variety of conditions inherent to chronic kidney disease (CKD) and to dialysis treatment. Skeletal muscle mass and function serve ...as indicators of the nutritional and clinical state of CKD patients, and low values or derangements over time are strong predictors of poor patient outcomes. However, muscle size and function can be affected by different factors, may decline at different rates, and may have different patient implications. Therefore, operational definitions of frailty and sarcopenia have emerged to encompass these 2 dimensions of muscle health, i.e., size and functionality. The aim of this review is to appraise available methods for assessment of muscle mass and functionality, with an emphasis on their accuracy in the setting of CKD patients. We then discuss the selection of reference cutoffs for defining conditions of muscle wasting and dysfunction. Finally, we review definitions applied in studies addressing sarcopenia and frailty in CKD patients and discuss their applicability for diagnosis and monitoring.
The relative importance of sarcopenia and its individual components as independent predictors of mortality in the dialysis population has not been determined. We estimated whole-body muscle mass ...using pre-dialysis bioimpedance spectroscopy measurements in 645 ACTIVE/ADIPOSE-enrolled prevalent hemodialysis patients from San Francisco and Atlanta. Low muscle mass was defined as two standard deviations below sex-specific means for young adults from NHANES and indexed to height2, body weight, body surface area, or body mass index. We evaluated the association of sarcopenia (low muscle mass) by four indexing methods, weak hand grip strength, and slow gait speed with mortality. Seventy-eight deaths were observed during a mean follow-up of 1.9 years. Sarcopenia was not significantly associated with mortality after adjusting for covariates. No muscle mass criteria were associated with death, regardless of indexing metrics. In contrast, having weak grip strength or slow walking speed was associated with mortality in the adjusted model. Only gait slowness significantly improved the predictive accuracy for death with an increase in C-statistic from 0.63 to 0.68. However, both gait slowness and hand grip weakness significantly improved the net reclassification index compared to models without performance measures (50.5% for slowness and 33.7% for weakness), whereas models with muscle size did not. Neither sarcopenia nor low muscle mass by itself was a better predictor of mortality than functional limitation alone in patients receiving hemodialysis. Thus, physical performance measures, including slow gait speed and weak hand grip strength, were associated with mortality even after adjustment for muscle size and other confounders.
Summary at a Glance
This review discusses the problem of insulin resistance in chronic kidney disease, including its assessment, causes, consequences and possible therapeutic management.
ABSTRACT
...This review provides an overview of insulin resistance (IR) in patients with chronic kidney disease (CKD). IR is a pathological state in which target tissues fail to respond normally to insulin. IR is understood as a consequence of CKD and its prevalence rises particularly in advanced CKD stages. Mechanisms leading to IR are complex and multifactorial, involving post‐receptor signaling defects, unhealthy lifestyles, metabolic acidosis, inflammation, oxidative stress, vitamin D deficiency, anemia, and uremic toxicity, as shown by human and experimental studies over the last 30 years. Whereas hyperinsulinemic euglycemic clamp is the gold standard, it is unpractical at the bedside, and either estimated IR indices by fasting glucose or insulin and oral glucose tolerance tests (OGTT) provide satisfactory estimates of IR also in patients with CKD. IR is likely to play a key role in the development of cardiometabolic complications, but not all studies associate IR with the risk of cardiovascular events and death. Various interventions at the level of lifestyle modifications, adaptations in dialysis therapy (such as use of icodextrin based solutions) and pharmacological strategies such as thiazolidinediones or vitamin D therapy may improve IR in patient with CKD.
Background and aims
Evidences on the benefits of physical exercise in kidney transplant patients (KTx) are not conclusive and concerns on safety remain. We here gather and interpret current evidence ...on the benefits/harms of exercise training intervention in KTx.
Methods
Systematic review of exercise training programs in KTx.
Results
A total of 24 studies including 654 KTx patients on intervention and 536 controls were evaluated. The median age was 46 years; the transplant vintage was 2 days to 10 years. The intervention was an aerobic or resistance exercise program or a combination of both; interventions consisted of 20–60 min’ sessions, 2–3 times per week repetitions and 5.5 months’ median duration. Most studies improved cardiorespiratory fitness (expressed as VO
2peak
) as well as maximum heart rate, which was associated with a significant increase in muscle performances and strength. No significant changes in body weight or composition were observed, but a trend towards weight reduction in overweight or obese patients on stable KTx was noted. The arterial blood pressure reduced a little after exercise when it was high at start. Exercise intervention had no clinically relevant impact on anaemia, glycaemia or lipidaemia. In contrast, exercise training improved several aspects of quality of life. No data on long-term hard outcomes or on high-risk subpopulations such comorbid or elderly patients were available.
Conclusions
In adult kidney transplant patients, a structured physical exercise program improved the aerobic capacity and ameliorated muscle performance and quality of life. No harms were observed in the short-term, but long-term RCTs are required. Overall, in mid-age kidney transplant patients without major comorbidities, an aerobic or resistance supervised exercise lasting 3–6 months could be suggested within the comprehensive treatment of kidney transplant.
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