CKD-related Complications Research Articles

Similar quality in chronic kidney disease multidisciplinary follow-up between kidney.

Introduction:Multidisciplinary clinics are the best approach towards Chronic Kidney Disease (CKD) patients in pre-dialysis phases. The few studies regarding kidney transplant recipients (KTR) compare multidisciplinary and non-multidisciplinary clinics.Methods:In this study, we compared the quality of multidisciplinary CKD care between 101 KTR and 101 propensity score-matched non-transplant pre-dialysis patients (PDP). Prevalence of patients without specific treatment at any time and percent time without specific treatment for CKD complications were the main outcomes and patient and kidney function survival, glomerular filtration rate (GFR) decline, prevalence of CKD-related complications, and percent time within therapeutic goals were the exploratory ones.Results:Time within most goals was similar between the groups, except for diastolic blood pressure (83.4 vs. 77.3%, RR 0.92, CI 0.88-0.97, p = 0.002) and hypertriglyceridemia (67.7 vs. 58.2%, OR 0.85, CI 0.78-0.93, p < 0.001), better in non-transplant PDP, and for proteinuria (92.7 vs. 83.5%, RR 1.1, CI 1.05-1.16, p < 0.001), better in KTR. Patient survival and GFR decline were similar between the groups, although non-transplant PDP tended to progress earlier to dialysis (9.9% vs. 6.9%, HR 0.39, p = 0.07, CI 0.14-1.08).Discussion:The similar findings between non-transplant PDP and KTR suggests that good and comparable quality of multidisciplinary is a valid strategy for promoting optimal clinical management of CKD-related complications in KTR.

A roadmap for optimizing chronic kidney disease patient care and patient-oriented research in the Eastern European nephrology community.

Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3–5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease–related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.

Prebiotic Therapy with Inulin Associated with Low Protein Diet in Chronic Kidney Disease Patients: Evaluation of Nutritional, Cardiovascular and Psychocognitive Parameters.

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)—with or without oral inulin supplementation as a prebiotic—modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case–control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus (p ≤ 0.01) and serum uric acid (p ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, p ≤ 0.01; base excess, p ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin (p = 0.008) and fasting glucose levels (p = 0.022), HOMA-IR (p = 0.004), as well as lower total serum cholesterol (p = 0.012), triglycerides (p = 0.016), C-reactive protein (p = 0.044) and homocysteine (p = 0.044) and higher HDL (p < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.

Serum Klotho, Cardiovascular Events, and Mortality in Nondiabetic Chronic Kidney Disease

Background: Experimental studies indicate that Klotho deficiency is a pathogenic factor for CKD-related complications, including cardiovascular disease (CVD). However, the association between serum Klotho and clinical outcomes in nondiabetic CKD patients needs to be further clarified. We aimed to determine whether serum Klotho levels are associated with CVD events and mortality in predialysis CKD patients without diabetes. Methods: A total of 336 CKD stage 2–5 predialysis patients without diabetes were recruited and followed from the end of 2014 to January 2019 for CVD events and overall mortality. Serum Klotho was detected by ELISA and divided into quartiles (lowest, middle, second highest, and highest quartiles) according to their serum Klotho category. Results: After a median follow-up of 3.52 years (IQR 3.34–3.76), Kaplan-Meier analysis showed that, compared to participants with a Klotho level in the highest quartile (the reference category), those in the lowest Klotho quartile were associated with a higher all-cause mortality risk (HR = 7.05; 95% CI 1.59–31.25) and a higher CVD event risk (HR = 3.02; 95% CI 1.45–6.30). In addition, the middle Klotho quartile was also associated with CVD event risk (HR = 2.56; 95% CI 1.21–5.41). Moreover, in the multivariate-adjusted model, the lowest Klotho quartile remained significantly associated with all-cause mortality (HR = 5.17; 95% CI 1.07–24.96), and the middle Klotho quartile maintained a significant association with CVD event risk (HR = 2.32; 95% CI 1.03–5.21). Conclusion: These results suggest that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients.

Effect of Low-Protein Diet and Inulin on Microbiota and Clinical Parameters in Patients with Chronic Kidney Disease.

Introduction: The gut microbiota has coevolved with humans for a mutually beneficial coexistence and plays an important role in health and disease. A dysbiotic gut microbiome may contribute to progression to chronic kidney disease (CKD) and CKD-related complications such as cardiovascular disease. Microbiota modulation through the administration of prebiotics may represent an important therapeutic target. Aim: We sought to evaluate the effects of a low-protein diet (LPD) (0.6 g/kg/day) with or without the intake of the prebiotic inulin (19 g/day) on microbiota and clinical parameters in CKD patients. Materials and Methods: We performed a longitudinal, prospective, controlled, and interventional study on 16 patients: 9 patients treated with LPD (0.6 g/kg/day) and inulin (19 g/day) and 7 patients (control group) treated only with LPD (0.6 g/kg/day). Clinical evaluations were performed and fecal samples were collected for a subsequent evaluation of the intestinal microbiota in all patients. These tests were carried out before the initiation of LPD, with or without inulin, at baseline (T0) and at 6 months (T2). The microbiota of 16 healthy control (HC) subjects was also analyzed in order to identify potential dysbiosis between patients and healthy subjects. Results: Gut microbiota of CKD patients was different from that of healthy controls. The LPD was able to significantly increase the frequencies of Akkermansiaceae and Bacteroidaceae and decrease the frequencies of Christensenellaceae, Clostridiaceae, Lactobacillaceae, and Pasteurellaceae. Only Bifidobacteriaceae were increased when the LPD was accompanied by oral inulin intake. We showed a significant reduction of serum uric acid (SUA) and C-reactive protein (CRP) in patients treated with LPD and inulin (p = 0.018 and p = 0.003, respectively), an improvement in SF-36 (physical role functioning and general health perceptions; p = 0.03 and p = 0.01, respectively), and a significant increase of serum bicarbonate both in patients treated with LPD (p = 0.026) or with LPD and inulin (p = 0.01). Moreover, in patients treated with LPD and inulin, we observed a significant reduction in circulating tumor necrosis factor alpha (TNF-α) (p = 0.041) and plasma nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) (p = 0.027) levels. We did not find a significant difference in the circulating levels of Interleukin (IL)-1β (p = 0.529) and IL-6 (p = 0.828) in the two groups. Conclusions: LPD, associated or not with inulin, modified gut microbiota and modulated inflammatory and metabolic parameters in patients with CKD. Our results suggest that interventions attempting to modulate the gut microbiome may represent novel strategies to improve clinical outcomes in CKD patients and may provide useful therapeutic effects.

A Pragmatic Cluster Randomized Trial of an Electronic Clinical Decision Support System to Improve Chronic Kidney Disease Management in Primary Care: Design, Rationale, and Implementation Experience.

BackgroundThe diagnosis of chronic kidney disease (CKD) is based on laboratory results easily extracted from electronic health records; therefore, CKD identification and management is an ideal area for targeted electronic decision support efforts. Early CKD management frequently occurs in primary care settings where primary care providers (PCPs) may not implement all the best practices to prevent CKD-related complications. Few previous studies have employed randomized trials to assess a CKD electronic clinical decision support system (eCDSS) that provided recommendations to PCPs tailored to each patient based on laboratory results.ObjectiveThe aim of this study was to report the trial design and implementation experience of a CKD eCDSS in primary care.MethodsThis was a 3-arm pragmatic cluster-randomized trial at an academic general internal medicine practice. Eligible patients had 2 previous estimated-glomerular-filtration-rates by serum creatinine (eGFRCr) <60 mL/min/1.73m2 at least 90 days apart. Randomization occurred at the PCP level. For patients of PCPs in either of the 2 intervention arms, the research team ordered triple-marker testing (serum creatinine, serum cystatin-c, and urine albumin-creatinine-ratio) at the beginning of the study period, to be completed when acquiring labs for regular clinical care. The eCDSS launched for PCPs and patients in the intervention arms during a regular PCP visit subsequent to completing the triple-marker testing. The eCDSS delivered individualized guidance on cardiovascular risk-reduction, potassium and proteinuria management, and patient education. Patients in the eCDSS+ arm also received a pharmacist phone call to reinforce CKD-related education. The primary clinical outcome is blood pressure change from baseline at 6 months after the end of the trial, and the main secondary outcome is provider awareness of CKD diagnosis. We also collected process, patient-centered, and implementation outcomes.ResultsA multidisciplinary team (primary care internist, nephrologists, pharmacist, and informaticist) designed the eCDSS to integrate into the current clinical workflow. All 81 PCPs contacted agreed to participate and were randomized. Of 995 patients initially eligible by eGFRCr, 413 were excluded per protocol and 58 opted out or withdrew, resulting in 524 patient participants (188 usual care; 165 eCDSS; and 171 eCDSS+). During the 12-month intervention period, 53.0% (178/336) of intervention patient participants completed triple-marker labs. Among these, 138/178 (77.5%) had a PCP appointment after the triple-marker labs resulted; the eCDSS was opened for 73.9% (102/138), with orders or education signed for 81.4% (83/102).ConclusionsSuccessful integration of an eCDSS into primary care workflows and high eCDSS utilization rates at eligible visits suggest this tailored electronic approach is feasible and has the potential to improve guideline-concordant CKD care.Trial RegistrationClinicalTrials.gov NCT02925962; https://clinicaltrials.gov/ct2/show/NCT02925962 (Archived by WebCite at http://www.webcitation.org/78qpx1mjR)International Registered Report Identifier (IRRID)DERR1-10.2196/14022

Gut Microbiota In Chronic Kidney Disease

Abstract In health, the relationship between gut microflora and the host is of a mutualistic kind. Microbiota offers many benefits to the host, including harvesting energy, regulating host immunity, and the synthesis of vitamins. Alteration in gut microflora can lead to homeostasis disruption and development of various diseases. Dysbiosis is commonly observed in chronic kidney disease (CKD). Nutrient processing by gut microbiota results in the production of some uremic toxins, and these accumulate in CKD causing deleterious effects. Increased permeability of the intestinal barrier, which is also seen in CKD contributes to the development of the uremic state. These factors are associated with chronic inflammation and oxidative stress and therefore are involved in CKD-related complications, including disease progression, cardiovascular disease, anemia, mineral-metabolism, and insulin resistance. This review describes connections between altered gut microflora and development of CKD and its complications, as well as possible therapeutic options. 1. Microbiota – short characteristic. 2. Mechanisms leading to alterations in gut microbiota and their effects on intestinal barrier permeability. 3. Causes of chronic kidney disease progression related to gut microbiota alterations. 4. Complications of chronic kidney disease related to gut microbiota alterations. 4.1. Cardiovascular disease. 4.2. Anemia. 4.3. Bone metabolism disorders. 4.4. Insulin resistance in CKD. 5. Therapeutic options. 6. Summary

PUK11 - ECONOMIC BURDEN OF CHRONIC KIDNEY DISEASE RELATED COMPLICATIONS AND THERAPIES IN CHINA: QUANTIFYING THE COSTS OF CARDIOVASCULAR EVENTS, BLOOD TRANSFUSION FOR ANEMIA AND DIALYSIS

Our objective was to estimate the costs of common chronic kidney disease (CKD)-related complications and therapies (cardiovascular (CV) events, blood transfusion for anemia, and dialysis) in China, for use in health economic analysis. This retrospective observational study used inpatient and outpatient insurance claims data from the China Health Insurance Research Association (CHIRA) in 2015. Adult patients with a CKD diagnosis were included. For patients with a hospitalization for CV events between 01/01/2015 and 30/09/2015, total inpatient costs per hospitalization were calculated, stratified by CV event type and dialysis status. Outpatient costs were determined for the three months post hospital discharge. Mean monthly costs before hospitalization were calculated for a patient subset with hospital admission after 01/04/2015. Furthermore, the cost of red blood cell transfusion (RBCT) during anemia-related hospitalizations was determined. Finally, monthly health care costs, including dialysis costs, were calculated for patients with ≥3 consecutive months with dialysis records. Among 31,886 CKD patients included in 2015, 2,871 patients had a CV hospitalization. The overall mean (median) cost per hospitalization was ¥14,488 (¥7871). Myocardial infarction was the costliest CV event (mean/median inpatient cost ¥29,203/¥13,046). Mean monthly outpatient costs per patient were higher post discharge (1st month: ¥264; 2nd month: ¥251; 3rd month: ¥228) than before the hospitalization (¥188.10; based on patient subset). Among the 1,227 patients with anemia-related hospitalizations with RBCT, the mean/median cost of blood products was ¥1,895/¥960 per patient per hospitalization. The 3,447 dialysis patients in our dataset incurred a mean/median monthly health care cost of ¥10,235/¥8,002 per patient, of which ¥5,874/¥5,240 were dialysis costs. Hemodialysis was more costly than peritoneal dialysis (mean/median monthly costs ¥6,096/¥5,348 vs. ¥3,861/¥3,939, respectively). Using high-quality insurance data from China, we quantified the costs of common CKD-related complications and therapies, which are major contributors to the economic burden of CKD.

Gut microbiota in chronic kidney disease

The intestinal microflora maintains a symbiotic relationship with the host under normal conditions, but its imbalance has recently been associated with several diseases.In chronic kidney disease (CKD), dysbiotic intestinal microflora has been reported with an increase in pathogenic flora compared to symbiotic flora. An enhanced permeability of the intestinal barrier, allowing the passage of endotoxins and other bacterial products to the blood, has also been shown in CKD. By fermenting undigested products that reach the colon, the intestinal microflora produce indoles, phenols and amines, among others, that are absorbed by the host, accumulate in CKD and have harmful effects on the body. These gut-derived uraemic toxins and the increased permeability of the intestinal barrier in CKD have been associated with increased inflammation and oxidative stress and have been involved in various CKD-related complications, including cardiovascular disease, anaemia, mineral metabolism disorders or the progression of CKD. The use of prebiotics, probiotics or synbiotics, among other approaches, could improve the dysbiosis and/or the increased permeability of the intestinal barrier in CKD.This article describes the situation of the intestinal microflora in CKD, the alteration of the intestinal barrier and its clinical consequences, the harmful effects of intestinal flora-derived uraemic toxins, and possible therapeutic options to improve this dysbiosis and reduce CKD-related complications.

Microbiota intestinal en la enfermedad renal crónica

The intestinal microflora maintains a symbiotic relationship with the host under normal conditions, but its imbalance has recently been associated with several diseases.In chronic kidney disease (CKD), dysbiotic intestinal microflora has been reported with an increase in pathogenic flora compared to symbiotic flora. An enhanced permeability of the intestinal barrier, allowing the passage of endotoxins and other bacterial products to the blood, has also been shown in CKD. By fermenting undigested products that reach the colon, the intestinal microflora produce indoles, phenols and amines, among others, that are absorbed by the host, accumulate in CKD and have harmful effects on the body. These gut-derived uraemic toxins and the increased permeability of the intestinal barrier in CKD have been associated with increased inflammation and oxidative stress and have been involved in various CKD-related complications, including cardiovascular disease, anaemia, mineral metabolism disorders or the progression of CKD. The use of prebiotics, probiotics or synbiotics, among other approaches, could improve the dysbiosis and/or the increased permeability of the intestinal barrier in CKD.This article describes the situation of the intestinal microflora in CKD, the alteration of the intestinal barrier and its clinical consequences, the harmful effects of intestinal flora-derived uraemic toxins, and possible therapeutic options to improve this dysbiosis and reduce CKD-related complications.

Metabolic profiles of the Flos Abelmoschus manihot extract by intestinal bacteria from the normal and CKD model rats based on UPLC-Q-TOF/MS.

Flos Abelmoschus manihot is a traditional herbal medicine widely used in clinical practice to tackle chronic kidney disease (CKD) for thousands of years. Nowadays, many studies indicate that gut bacteria are closely related to the progression of CKD and CKD-related complications. In this study, a UPLC-Q-TOF/MS method coupled with the MetaboLynx™ software was established and successfully applied to investigate the metabolites and metabolic profile of Flos A. manihot extract by intestinal bacteria from normal and CKD rats. Eight parent components and eight metabolites were characterized by their protonated ions. Among these compounds, 15 were detected in the two group samples while M16 was only determined in the CKD model samples. Compared with the quercetin-type glycosides, fewer myricetin-type and gossypetin-type metabolites were obtained in the two group samples. These metabolites suggested that deglycosylation and methylation are the major metabolic pathways of Flos A. manihot extract. Few differences of metabolite classes were observed in the two group samples. However, the concentrations of aglycones such as quercetin, myricetin and gossypetin in the normal samples were notably higher than those in the CKD model samples. The results are important in unravelling the pharmacological effects of A. manihot and clarifying its mechanism of action in vivo.

Fractional Excretion of Survivin, Extracellular Matrix Metalloproteinase Inducer, and Matrix Metalloproteinase 7 in Children with Chronic Kidney Disease

Background: Epithelial–mesenchymal transition (EMT) is defined as a transformation of tubular epithelial cells into mesenchymal ones. These cells migrate through the extracellular matrix and change into active myofibroblasts, which are responsible for excessive matrix deposition. Such changes may lead to tubular dysfunction and fibrosis of the renal parenchyma, characteristic of chronic kidney disease (CKD). However, there are no data on potential EMT markers in children with CKD. The aim of our study was to assess the usefulness of fractional excretion (FE) of survivin, E-cadherin, extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase (MMP)7, and transforming growth factor beta 1 (TGF-β1) as potential markers of CKD-related complications such as tubular damage and fibrosis. Methods: Forty-one pre-dialysis children with CKD Stages 3–5 and 23 age-matched controls were enrolled in the study. The serum and urine concentrations of analysed parameters were assessed by an enzyme-linked immunosorbent assay test. Results: Tubular reabsorption of all analysed parameters was &gt;99% in the control group. All FE values rose significantly in children with CKD, yet they remained &lt;1% in the case of E-cadherin and TGF-β1. The highest FE values in CKD children were those of survivin, EMMPRIN, and MMP7: &gt;1%. Conclusions: FE of the examined markers may become a useful tool in the assessment of tubular dysfunction during the course of CKD. The FE of survivin, EMMPRIN, and MMP7 warrant further research as potential independent markers of kidney-specific EMT.

Association of anemia and mineral and bone disorder with health-related quality of life in Asian pre-dialysis patients.

BackgroundPatients with chronic kidney disease (CKD) have poor health-related quality of life (HRQoL). The association of CKD-related complications such as anemia and mineral and bone disorders (MBD) with HRQoL in pre-dialysis patients is not well-studied. As such, this study aimed to determine the association of anemia and MBD with HRQoL in pre-dialysis patients.MethodsThis was a cross-sectional study involving 311 adult pre-dialysis patients with stage 3–5 CKD from an acute-care hospital in Singapore. Patients’ HRQoL were assessed using Kidney Disease Quality of Life Short Form (KDQOL-SF™) and EuroQol 5 Dimensions–3 levels (EQ5D-3L). HRQoL between patients with and without anemia or MBD were compared by separate hierarchical multiple linear regression analyses using various HRQoL scales as dependent variables, adjusted for sociodemographic, clinical and psychosocial variables.ResultsAfter adjusting for MBD, anemia was associated with lower HRQoL scores on work status (WS), physical functioning (PF) and role physical [β (SE): −10.9 (4.18), p = 0.010; −3.0 (1.28), p = 0.018; and −4.2 (1.40), p = 0.003, respectively]. However, significance was lost after adjustments for sociodemographic variables. Patients with MBD had poorer HRQoL with respect to burden of kidney disease, WS, PF and general health [(β (SE): −7.9 (3.88), p = 0.042; −9.5 (3.99), p = 0.018; −3.0 (1.22) p = 0.014; −3.6 (1.48), p = 0.015, respectively]. Although these remained significant after adjusting for sociodemographic variables, significance was lost after adjusting for clinical variables, particularly pill burden. This is of clinical importance due to the high pill burden of CKD patients, especially from medications for the management of multiple comorbidities such as cardiovascular and mineral and bone diseases.ConclusionsNeither anemia nor MBD was associated with HRQoL in our pre-dialysis patients. Instead, higher total daily pill burden was associated with worse HRQoL. Medication reconciliation should therefore be routinely performed by clinicians and pharmacists to reduce total daily pill burden where possible.

Prevalence and complications of chronic kidney disease in a representative elderly population in Iceland.

Chronic kidney disease (CKD) is common in the elderly, but data are limited on the distribution of glomerular filtration rate (GFR) and albuminuria and the prevalence of CKD and related complications in this population. A cross-sectional study of 3173 older Icelandic adults [42% men; mean (standard deviation, SD) age of 80 (5) years] was performed to examine the distribution of estimated glomerular filtration rate (eGFR) from creatinine and cystatin C, the albumin-to-creatinine ratio (ACR), and CKD-related metabolic complications (hyperparathyroidism, anemia, hypoalbuminemia, increased anion gap, acidosis, hyperphosphatemia and hyperkalemia). There was substantial variability in eGFR [mean (SD) 64 (18) mL/min/1.73 m(2)] and ACR [median (interquartile range) 8 (5, 17) mg/g]. The prevalence (95% confidence interval) of reduced eGFR (<60 mL/min/1.73 m(2)), albuminuria (ACR >30 mg/g) and CKD (either reduced eGFR or albuminuria) was 40% (38-41), 14% (12-15) and 45% (43-47), respectively. The prevalence of complications was higher among those with versus without CKD: hyperparathyroidism (38 versus 15%), anemia (26 versus 14%), hypoalbuminemia (19 versus 13%), increased anion gap (9 versus 5%), acidosis (5 versus 1%); (P ≤ 0.02 for all), except hyperphosphatemia (1 versus 1%) and hyperkalemia (0% overall). The burden of CKD and CKD-related complications is high among community dwelling elderly Icelandic adults. The wide range of eGFR and ACR suggests heterogeneity in processes leading to CKD and that factors beyond aging contribute to the development of CKD in the elderly.

Influence of Nephrologist Care on Management and Outcomes in Adults with Chronic Kidney Disease.

Predialysis nephrology care for adults with late stage chronic kidney disease (CKD) is associated with improved outcomes. Less is known about the effects of nephrology care in earlier stages of CKD. We aimed to evaluate the effect of nephrology care on management of CKD risk factors and complications, CKD progression, incident cardiovascular disease (CVD), and death. This was a prospective cohort study. Participants included 3855 men and women aged 21 to 74 years enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study with a mean (SD) estimated glomerular filtration rate (eGFR) at entry of 45 (17) ml/min/1.73 m(2), followed for a median of 6.6 years. The main predictor was self-reported prior contact with a nephrologist at study enrollment. Outcomes evaluated included CKD progression (≥ 50 % eGFR loss or end-stage renal disease), incident CVD, and death. Two-thirds (67 %) of the participants reported prior contact with a nephrologist at study enrollment. They were younger, more likely to be male, non-Hispanic white, and had lower eGFR and higher urine protein (p < 0.05). A subgroup with eGFR 30- < 60 ml/min/1.73 m(2) and prior contact with a nephrologist were more likely to receive pharmacologic treatment for CKD-related complications and to report angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) use. After propensity score matching (for reporting prior contact with a nephrologist vs. not) and adjusting for demographic and clinical variables, prior contact with a nephrologist was not significantly associated with CKD progression, incident CVD or death (p > 0.05). One-third of CRIC participants had not seen a nephrologist before enrollment, and this prior contact was subject to age, sex, and ethnic-related disparities. While prior nephrology care was associated with more frequent treatment of CKD complications and use of ACEi/ARB medications, there was neither an association between this care and achievement of guideline-recommended intermediate measures, nor long-term adverse outcomes.

High Intensity Interval Training Favourably Affects Angiotensinogen mRNA Expression and Markers of Cardiorenal Health in a Rat Model of Early-Stage Chronic Kidney Disease.

The majority of CKD-related complications stem from cardiovascular pathologies such as hypertension. To help reduce cardiovascular complications, aerobic exercise is often prescribed. Emerging evidence suggests high intensity interval training (HIIT) may be more beneficial than traditional aerobic exercise. However, appraisals of varying forms of aerobic exercise, along with descriptions of mechanisms responsible for health-related improvements, are lacking. This study examined the effects of 8 weeks of HIIT (85% VO2max), versus low intensity aerobic exercise (LIT; 45–50% VO2max) and sedentary behaviour (SED), in an animal model of early-stage CKD. Tissue-specific mRNA expression of RAAS-related genes and CKD-related clinical markers were examined. Compared to SED, HIIT resulted in increased plasma albumin (p = 0.001), reduced remnant kidney weight (p = 0.028), and reduced kidney weight-body weight ratios (p = 0.045). Compared to LIT, HIIT resulted in reduced Agt mRNA expression (p = 0.035), reduced plasma LDL (p = 0.001), triglycerides (p = 0.029), and total cholesterol (p = 0.002), increased plasma albumin (p = 0.047), reduced remnant kidney weight (p = 0.005), and reduced kidney weight-body weight ratios (p = 0.048). These results suggest HIIT is a more potent regulator of several markers that describe and influence health in CKD.

Re-evaluating the predictive roles of metabolic complications and clinical outcome according to eGFR levels — a four-years prospective cohort study in Taiwan

BackgroundMetabolic complications are associated with clinical outcomes in patients with chronic kidney disease (CKD). These outcomes differ among patients according to the different stages of disease. The prevalence and association of type and number of metabolic complications with renal progression and death in patients having different eGFR levels has high clinical value, but this fact has been rarely evaluated in prospective studies.MethodsWe prospectively followed a cohort of 1157 CKD patients from 2006 to death or until 2010, and evaluated the prevalence of CKD-related complications and their association with renal progression (defined as a decline in eGFR by > 50% from baseline, or end-stage renal disease requiring dialysis) and death in patients with eGFRs above and below 45 mL/min/1.73 m2 using Cox-proportional hazard models.ResultsThe estimated rate (per 100 patient-years) of renal progression and death were 11.9 and 4.9, respectively. The eGFR thresholds determined by ROC analysis with a sensitivity of 90% for any metabolic complication were 60.8 mL/min/1.73 m2 and 74.3 mL/min/1.73 m2 using the MDRD and CKD Epidemiology Collaboration equations, respectively. CKD-related complications associated with renal progression in patients having eGFR < 45 mL/min/1.73 m2 were hyperphosphatemia, anemia, microinflammation and hypoalbuminemia. Those CKD-related complications associated with death were hypoalbuminemia and hyperuricemia. Hypoalbuminemia predicted renal progression, and, hypoalbuminemia and microinflammation predicted death in patients with eGFR ≥ 45 mL/min/1.73 m2. The number of complications (≥ 3) independently predicted both endpoints in patients with eGFR < 45 mL/min/1.73 m2.ConclusionsHypoalbuminemia was a unique and strong predictor of renal progression and all-cause mortality in CKD patients, independent of their demographic characteristics, traditional risk factors, renal function severity, the presence of cardiovascular disease and other metabolic abnormalities. Most other metabolic complications and the number of complications (≥3) were associated with the clinical outcomes of patients with eGFR < 45 mL/min/1.73 m2 rather than in those with higher eGFRs. The findings from the present study offer a novel insight into the association between metabolic complications and patient outcomes and may help to refine risk stratification according to disease stage.

The prevalence and detection of chronic kidney disease (CKD)-related metabolic complications as a function of estimated glomerular filtration rate in the oldest old

BackgroundThe prevalence of CKD rises with age. The prevalence of CKD-related metabolic complications in the oldest old in relation to different GFR estimations is largely unknown. eGFR-based thresholds for the detection of these complications remain uncertain. MethodsA cross-sectional analysis embedded within the BELFRAIL study, a population-based prospective cohort study of the oldest old in Belgium, was performed. The prevalence of anemia, elevated serum parathyroid hormone (PTH), high serum phosphorus and low uncorrected serum calcium was analyzed in relation to GFR estimated by three serum creatinine-based equations and one cystatin C-based equation. Results567 patients aged 80 and over were included (63% women). The prevalence of anemia, elevated PTH and high phosphorus showed an inverse relationship with eGFR. This relationship remained after logistic regression analysis adjusting for demographics and co-morbidity. No such relationship between low calcium and eGFR was found. Using an eGFR of 60ml/min/1.73m2 modification of diet in renal disease equation (MDRD) as screening threshold for metabolic complications would result in a high incidence of missed complications: 29%, 28% and 40% for anemia, elevated PTH and high phosphorus, respectively. ConclusionThe presence of anemia, an elevated PTH or an elevated serum phosphorus level increased with lower eGFR but even among patients with an eGFR >60ml/min/1.73m2, these complications are common. Thus this eGFR cut-off appears inadequate for patients aged 80 and over. How the oldest old may be screened appropriately for these CKD-related complications requires further investigation.

Measured GFR Does Not Outperform Estimated GFR in Predicting CKD-related Complications

Although many assume that measurement of glomerular filtration rate (GFR) using a marker such as iothalamate (iGFR) is superior to equation-estimated GFR (eGFR), each of these methods has distinct disadvantages. Because physicians often use renal function to guide the screening for various CKD-associated complications, one method to compare the clinical utility of iGFR and eGFR is to determine the strength of their association with CKD-associated comorbidities. Using a subset of 1214 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study, we determined the cross-sectional associations between known complications of CKD and iGFR, eGFR estimated from serum creatinine (eGFR_Cr), and eGFR estimated from cystatin C (eGFR_cysC). We found that none of the measures of renal function strongly associated with CKD complications and that the relative strengths of associations varied according to the outcome of interest. For example, iGFR demonstrated better discrimination than eGFR_Cr and eGFR_cysC for outcomes of anemia and hemoglobin concentration; however, both eGFR_Cr and eGFR_cysC demonstrated better discrimination than iGFR for outcomes of hyperphosphatemia and phosphorus level. iGFR and eGFR had similar strengths of association with hyperkalemia/potassium level and with metabolic acidosis/bicarbonate level. In conclusion, iothalamate measurement of GFR is not consistently superior to equation-based estimations of GFR in explaining CKD-related comorbidities. These results raise questions regarding the conventional view that iGFR is the "gold standard" measure of kidney function.

Is There Something Better than the Best Marker of Kidney Function?

Measurement of kidney function is critical both for clinical decision-making and research. Direct measurement of GFR using urinary or plasma clearance of exogenously administered markers, such as 125I-iothalamate, is considered the gold standard method to assess kidney function. These procedures,