Late-stage Chronic Kidney Disease Patients Research Articles

Pharmacological interventions improve myosin-actin cross-bridge function in mice with advanced chronic kidney disease.

Skeletal muscle fiber force production in adult mice with late-stage chronic kidney disease (CKD) is significantly impaired, although by different myofilament and myosin-actin cross-bridge disease responses in the various fiber types. To reverse some of the CKD-induced contractile deficits, we examined the effects of the ATP analog, 2-deoxyadenosine triphosphate (dATP), to enhance cross-bridge kinetics and the troponin sensitizer, Tirasemtiv (2 µM), to increase cross-bridge formation. Single fiber force production, myosin-actin interactions and myofilament properties were measured at 25°C in fibers from soleus and extensor digitorum longus muscles of 16-week-old CKD mice (N=5) and controls (N=5). Late-stage CKD was induced by 0.2% adenine diet for 8 weeks. dATP in myosin heavy chain (MHC) I and IIA fibers with CKD increased cross-bridge kinetics, returning them to control values or faster, leading to more strongly bound cross-bridges for maximal Ca2+-activation (pCa 4.5, pH 7.0, 5 mM Phosphate) and fatiguing (pCa 4.5, pH 6.2, 30 mM Phosphate) conditions. Specific tensions in CKD were also improved 12-21% under maximal and fatiguing conditions, except in maximally Ca2+-activated MHC I fibers, but fell short of control values. Notably, other studies have found that improvements of 13-25% in knee extensor strength in CKD patients improved their physical function, suggesting changes of this magnitude are clinically meaningful. At submaximal Ca2+-activation (pCa 6.0), Tirasemtiv in MHC IIB fibers with CKD increased myofilament stiffness 520%, number of strongly bound cross-bridges 705%, and specific tension 370%, returning specific tension back to control values. This study provides evidence that cellular and molecular contractile function in CKD may be enhanced through use of dATP or Tirasemtiv, which should be tested to potentially improve physical function and overall quality of life in late-stage CKD patients.

Iron supplementation improves skeletal muscle contractile properties in mice with chronic kidney disease.

Adult chronic kidney disease (CKD) patients commonly display decreased physical function, leading to increased mortality, which is exacerbated with iron deficiency and anemia. Interventions to mitigate CKD myopathy are scarce, potentially because the underlying contractile deficits have not been fully investigated. We examined single fiber force production, myosin-actin interactions and myofilament properties in soleus and extensor digitorum longus muscles of 16-week-old CKD mice without (CKD, N=12) and with iron supplementation (CKDFE, N=6, weekly injections of 0.2 mg/kg iron dextran) and controls (N=10). Late-stage CKD was induced by 0.2% adenine diet for 8 weeks. CKD with iron supplementation (CKDFE) improved anemia status compared to CKD, but not back to control levels. Maximally activated (pCa 4.5, 25°C) specific tension (maximal isometric force divided by cross-sectional area) was reduced 36-51% with CKD due, in a large part, to a reduction in strongly-bound myosin-actin cross-bridges in all myosin heavy chain (MHC) I, IIA, and IIB fibers. Iron supplementation improved specific tension and number of strongly-bound cross-bridges in MHC IIA and IIB fibers. Myosin-actin cross-bridge kinetics were slower with CKD in MHC I and IIA fibers, with iron supplementation restoring kinetics closer to control values in MHC IIA fibers. Higher hemoglobin levels were correlated to improvements in specific tension and strongly-bound cross-bridges in MHC IIA and IIB fibers, and with faster cross-bridge kinetics in MHC IIA fibers. However, CKD induced decreases in myofilament lattice stiffness for MHC IIA and IIB fibers were not improved with iron supplementation. Our findings show that iron supplementation improved various aspects of the cellular and molecular CKD-induced myopathy in fast-contracting fiber types. Thus, correction of iron imbalance and/or anemia may be an effective countermeasure to reduce contractile deficits and improve quality of life in late-stage CKD patients.

Comparison of antibody response following the second dose of SARS-CoV-2 mRNA vaccine in elderly patients with late-stage chronic kidney disease

BackgroundCurrently, it is unclear whether the progression of chronic kidney disease (CKD) could be an independent predictor of antibody response after administration of a COVID-19 vaccine. This study aimed to investigate the immune response to COVID-19 vaccination in patients with CKD stage G4 to G5 without renal replacement therapy and G5D using the recommended dose and schedule.MethodsThis retrospective single-center cohort study evaluated immunogenicity regarding antibody response after COVID-19 vaccination in our hospital for late-stage CKD patients aged ≥ 60 years. We evaluated antibody responses in 48 patients with CKD G4, 35 patients with CKD G5, and 70 patients undergoing hemodialysis (HD; CKD G5D).ResultsAfter the second vaccination, anti-SARS-CoV-2-S (Spike) IgG levels were found to be positive (> 0.8 U/mL) in all CKD G4 and G5 patients (100%), and 69 of 70 HD patients (98.5%). The median (interquartile range [IQR] S-IgG level (Ab titers) was 358 [130.2–639.2], 218 [117–377], and 185.5 [95.1–323.5] U/mL in the CKD G4, G5, and HD groups, respectively. The median S-IgG levels were significantly lower in the HD group than in the CKD G4 group (p < 0.01). However, there was no significant difference in the antibody titers between the CKD G4 and G5 groups. To further analyze the decline in S-IgG levels after 6 months, we additionally assessed and compared antibody titers at 1 month and 6 months after the second vaccination in the HD group. Compared with the median S-IgG levels of 185.5 [95.1–323.5] U/mL 1 month after the second dose, the median S-IgG level 6 months thereafter was significantly decreased at 97.4 [62.5–205.5] U/mL (p < 0.05).ConclusionsWe highlight two major factors of variability in the vaccine response. First, in elderly patients with late-stage CKD, antibody titers tended to be lower in the G5D group than in the G4 and G5 groups despite the shorter time since vaccination; therefore, CKD stage progression might cause a decline in antibody titers. Second, waning immune responses were observed 6 months after second dose administration in HD patients advocating a potential need for a third booster dose vaccine after 6 months.

Prevalence and Significance of Pyuria in Chronic Kidney Disease Patients in Saudi Arabia.

Chronic kidney disease (CKD) is considered a major health problem, which poses a burden for health care systems worldwide. It has been estimated that 10% of the population worldwide have CKD; however, most of the cases are undiagnosed. If left untreated, CKD could lead to kidney failure, which highlights the importance of early diagnosis and treatment. Pyuria has been reported in CKD patients, and could be the result of several comorbidities, such as diabetes, or urinary tract infections (UTIs). A few studies have shown that pyuria is associated with the late stages of CKD. However, there are limited data on the prevalence of non-UTI (sterile) and UTI–pyuria in different CKD patient populations, and its association with the decline in kidney function and progression of CKD. In this retrospective study, we report the prevalence of pyuria (sterile and UTI) in 754 CKD patients of King Fahd Specialist Hospital, Buraydah, Saudi Arabia. Our data showed that 164/754 CKD patients (21.8%) had pyuria, whereas 590 patients (78.2%) presented with no pyuria. There was a significantly higher percentage of late-stage (stage 4) CKD patients in the pyuric group compared to the non-pyuric group (36.6% vs. 11.9%). In line with the previous data, proteinuria was detected in a significantly higher percentage of pyuric patients, in addition to significantly higher levels of serum creatinine and urea, compared to non-pyuric patients. Furthermore, 13.4% of the pyuric CKD patients had UTI, whereas 86.6% presented with sterile pyuria. E. coli was indicated as the causative agent in 45.5% of UTI patients. Our patient data analysis showed that a significantly higher percentage of UTI–pyuric CKD patients, than sterile pyuric patients (63.6% vs. 19.7%), had higher numbers of urinary white blood cells (>50/HPF, WBCs). The data also showed that a higher percentage of UTI–pyuric patients were late-stage CKD patients, compared to sterile pyuric patients (50% vs. 34.5%). Our findings indicate that a high level of pyuria could be considered as a marker for late-stage CKD, and that UTI is an important risk factor for the decline in kidney function and the progression to late-stage CKD. We believe that further studies are needed to correlate pyuria to kidney function, which could be helpful in monitoring the progression of CKD. Moreover, the management of comorbidities, such as diabetes and UTIs, which are risk factors for CKD and associated pyuria, could help to control the progression of CKD to the late stages.

Impact of chronic kidney disease severity on causes of death after first-ever stroke: A population-based study using nationwide data linkage.

BackgroundStroke is prevalent in patients with chronic kidney disease (CKD) and is associated with high mortality, but the causes of death after stroke among different CKD stages are not well known.AimsWe aimed to investigate whether the severity of CKD would impact on the causes of death after first-ever stroke.MethodsThis retrospective multicenter cohort study included stoke patients with CKD between 2007 and 2012. The cause of death and date of death were ascertained by linking the National Death Registry Database of Taiwan. Clinical outcomes, 1-month, and 1-year mortality rates, and major causes of death were compared according to five CKD stages (G1 to G5) in the ischemic and hemorrhagic stroke separately.ResultsOf these patients, 9,878 were first-ever ischemic stroke (IS) patients, and 1,387 were first-ever hemorrhagic stroke (HS) patients. Patients with CKD G5 had the highest one-year mortality rate with hazard ratio 5.28 [95%CI, 3.94–7.08] in IS and 3.03 [95%CI, 2.03–4.54] in HS when compared to G1 patients. Leading causes of one-year death after IS were stroke, cancer, and pneumonia in early (G1-3) CKD patients, while diabetes mellitus, CKD, and stroke itself contributed to the major mortality in CKD G5 patients. An inverse association between eGFR decrement and the proportion of deaths caused by stroke itself was observed in CKD G2-5 patients after IS. Stroke was the leading cause of one-year death among all CKD patients after HS.ConclusionsAsides from high mortality, late-stage CKD patients had different causes of death from early CKD patients after stroke. This study highlights the need to imply different treatment strategies in late-stage CKD post-stroke patients to improve their prognosis.

Electrocardiographic abnormalities among late-stage non-dialysis chronic kidney disease patients.

Cardiovascular disease (CVD) complication is common among chronic kidney disease (CKD) patients. Thus, knowledge about CVD and ECG abnormalities in CKD are essential due to progressive nature of the disease and increased risk of sudden cardiac death. This study aims to scrutinize the ECG abnormalities among nondialysis late-stage CKD patients. A descriptive observational study was conducted at Dr. Soetomo General Hospital, Surabaya, Indonesia. Subjects were hospitalized patients with late-stage CKD between 1 January and 31 December 2019, who were consulted at the department of cardiology and vascular medicine during their initial admission at emergency room. ECG interpretation for this study was done by qualified cardiologist. There were 191 patients included in this study. Mean ages were 52.2±11.8 years old and 51% were males. Total 143 (74.9%) patients had anemia, 111 (58.1%) had hypertension and 75 (39.3%) had type 2 diabetes mellitus. Mean serum creatinine was 10.5±8.0mg/dL. There were 176 (92.1%) patients with at least one form of ECG abnormalities. Prolonged QTc interval (36.6%), fragmented QRS complex (29.8%), poor R wave progression (24.6%), peaked T wave (22.0%) and left ventricular hypertrophy (16.7%) were the most common abnormalities. ECG abnormalities are common among nondialysis late-stage CKD patients. Given the fact that long-term CKD influences the pathogenesis cardiovascular diseases and substantial cardiovascular mortality, there is a need to screen Indonesian CKD patients who are at risks of getting earlier complications.

Abstract 104: Mortality Risk Across Chronic Kidney Disease Stages With Fibrate or Niacin Use Compared With No Fibrate or Niacin Therapy in Male US Veterans

Background: Chronic kidney disease (CKD) patients have a higher cardiovascular (CV) disease and mortality risk, elevated triglycerides (TG), and decreased high density lipoproteins (HDL). Post-hoc analysis of trials examining use of fibrate (Fib) or niacin (Nia) therapy in lowering CV outcome risk have failed to show benefit in mild to moderate kidney disease. These analyses were criticized for their study design or small sample size. We sought to examine if Fib or Nia use is associated with lower mortality risk in US veterans across CKD stages. Methods: In a retrospective cohort analysis, we identified male veterans who initiated Fib or Nia, with a high TG ≥150 mg/dL or low HDL ≤40 mg/dL between 2004-2014, and matched them on CKD stage and TG and HDL levels to unexposed men. We examined the association of Fib or Nia use (ref: unexposed) with 12-month all-cause mortality risk across CKD stage strata using an adjusted Cox proportional hazards model. Propensity scores (PS) included baseline demographics, comorbidities and lab measures and high-dimensional propensity scores (HDPS) included over 100 covariates for each drug and stage analysis. PS and HDPS analyses included score adjustment and matching. Results: The cohort had a mean±SD age of 64±12 years, and 30% had CKD stage 3A and higher. There were 69,295 Fib, 87,727 Nia, and 114,411 unexposed patients, respectively. Patient characteristics were similar across drug groups within each CKD stage. With covariate adjustment, both Fib and Nia were associated with a lower death risk compared to unexposed men in lower CKD stages (Figure A and B). Among those with CKD stage 4/5, Fib and Nia were associated with a higher death risk (HR[95%CI]: 1.43[1.15, 1.78] and 1.17[0.97,1.40], respectively). Those on Fib or Nia and in end-stage renal disease had a null association with mortality. Associations were similar for each CKD stage in PS and HDPS analyses, yet Fib and Nia were no longer associated with a lower death risk for CKD stage 3A and 3B patients. Conclusion: Mortality associations of Fib and Nia among male veterans with high TG and low HDL varied across CKD stage, where CKD stage 4/5 patients had a higher mortality risk, even in PS and HDPS analyses. While covariate balance was met, further studies are needed to examine the mechanisms for this higher observed risk in late-stage CKD patients.

MON-155 COMPARITIVE ASSESSMENT OF PSYCHOSOCIAL NEEDS OF DIALYSIS PATIENTS WITH CHRONIC KIDNEY DISEASE AND PREDIALYSIS PATIENTS - A SINGLE CENTRE STUDY

As chronic disease sufferers, dialysis and late-stage chronic kidney disease patients are at a high risk of psychological as well as physical co-morbidities of their illness. Mental illnesses such as depression and anxiety are a significant burden in end-stage renal disease patients and are associated with poorer outcomes in physical health. Furthermore, poor physical health impacts ability to carry out activities of daily living. This has a negative impact on quality of life for many patients and few centres offer specific social or psychological support for this group. This cross-sectional survey-based study seeks to evaluate objective and subjective indicators of health-related quality of life, and to identify predictors of poor physical and mental health in a population of severe end stage renal disease patients at a single centre without such support available. Following a pilot in dialysis patients only, 108 dialysis, 47 pre-dialysis (CKD5) and 55 chronic kidney disease stage 4 (CKD4) patients aged 18+ were surveyed when attending the unit for dialysis or an appointment, and by post if dialysing at home. The self-administered questionnaire reviewed the patient experience of dialysis/treatment, a self-assessment of ‘coping’ (scored out of 10) and need for additional support. Health-related quality of life (HR-QuOL) was assessed with the 12-Item Short Form Survey (SF-12) and scored using items 1-12 of the UCLA Kidney Disease Quality of Life v1.3 template to obtain scores of mental (MCS-12) and physical (PCS-12) health. Demographic associations with MCS-12 and PCS-12 were assessed by ANOVA with Bonferroni post-hoc correction and stepwise regression analysis. PCS-12 deteriorated with disease stage such that CKD4 patients had significantly greater scores than dialysis patients (p=.004); within the dialysis subgroup, PCS-12 was greater in PD than HD patients, but there was no significant difference between those treated at home and in the unit. Gender was found to be a predictor of MCS-12, where males generally exhibited better scores (p=.022). Self-assessed mental coping was lower in younger dialysis patients; however, there was no difference in HR-QuOL scores between age groups. Both MCS-12 and PCS-12 were most strongly predicted by the patient’s self-assessment ‘coping’ score /10 for their mental and physical health respectively Subjective patient reporting of their physical and mental health via a score from 1-10 gives a very strong indication of formal HR-QuOL score and may be a useful tool in practice to easily identify patients in need of support. Physical health score is best predicted by stage in disease process and, in dialysis groups, method of dialysis; mental health is best predicted by gender and to a lesser extent, age. By being aware of at-risk groups, identified in this cohort as the young, females, and patients with more advanced disease, specific services can be offered to improve quality of life through emotional and practical support. The authors hope to use the results of this study along with further analysis of patient-evaluated need to establish a renal-specific counselling service for those service users identified as in need of psychological and practical support.

Application of differential mobility-mass spectrometry for untargeted human plasma metabolomic analysis.

Differential mobility spectrometry (DMS) has been gaining popularity in small molecule analysis over the last few years due to its selectivity towards a variety of isomeric compounds. While DMS has been utilized in targeted liquid chromatography-mass spectrometry (LC-MS), its use in untargeted discovery workflows has not been systematically explored. In this contribution, we propose a novel workflow for untargeted metabolomics based solely on DMS separation in a clinically relevant chronic kidney disease (CKD) patient population. We analyzed ten plasma samples from early- and late-stage CKD patients. Peak finding, alignment, and filtering steps performed on the DMS-MS data yielded a list of 881 metabolic features (unique mass-to-charge and migration time combinations). Differential analysis by CKD patient group revealed three main features of interest. One of them was putatively identified as bilirubin based on high-accuracy MS data and comparison of its optimum compensation voltage (COV) with that of an authentic standard. The DMS-MS analysis was four times faster than a typical HPLC-MS run, which suggests a potential for the utilization of this technique in screening studies. However, its lower separation efficiency and reduced signal intensity make it less suitable for low-abundant features. Fewer features were detected by the DMS-based platform compared with an HPLC-MS-based approach, but importantly, the two approaches resulted in different features. This indicates a high degree of orthogonality between HPLC- and DMS-based approaches and demonstrates the need for larger studies comparing the two techniques. The workflow described here can be adapted for other areas of metabolomics and has a value as a prescreening method to develop semi-targeted workflows and as a faster alternative to HPLC in large biomedical studies.

Inflammation induces osteoclast differentiation from peripheral mononuclear cells in chronic kidney disease patients: crosstalk between the immune and bone systems.

Inflammation and immune system alterations contribute to bone damage in many pathologies by inducing the differentiation of osteoclasts (OCs), the bone resorbing cells. This link is largely unexplored in chronic kidney disease (CKD) and haemodialysis (HD) patients, in which reduced renal function is accompanied by an increased inflammatory state and skeletal abnormality. We used ex vivo culture experiments to investigate the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) of CKD and HD patients, focusing on immune cell subsets and inflammatory cytokines such as LIGHT and receptor activator of nuclear factor κB ligand (RANKL). We observed spontaneous osteoclastogenesis with a significant increase in OC formation and bone resorbing activity in late-stage CKD and HD patients when compared with early-stage CKD patients and healthy donors, likely due to an increased expression of RANKL and LIGHT (homologous to Lymphotoxins exhibiting Inducible expression and competing with herpes simplex virus Glycoprotein D for herpes virus entry mediator [HVEM], a receptor expressed by T lymphocytes) in PBMCs. Specific inhibition of these cytokines in PBMCs isolated from CKD stages 3b-5 and HD patients induced the reduction of OC formation in vitro. The phenotypic characterization of peripheral blood cells revealed a significant increase of OC precursors (CD14+CD11b+CD51/61+) and CD14+CD16+ monocytes in advanced CKD and HD patients compared with the control group. Our results suggest that circulating inflammatory monocytes from advanced CKD or HD patients trans differentiate into OCs in vitro and play a relevant role in mineral bone disorders and that LIGHT and RANKL represent new potential therapeutic targets in these settings.

Prognostic significance of pre-end-stage renal disease serum alkaline phosphatase for post-end-stage renal disease mortality in late-stage chronic kidney disease patients transitioning to dialysis.

Higher serum alkaline phosphatase (ALP) levels have been associated with excess mortality in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD). However, little is known about the impact of late-stage NDD-CKD ALP levels on outcomes after dialysis initiation. Among 17732 US veterans who transitioned to dialysis between October 2007 and September 2011, we examined the association of serum ALP levels averaged over the last 6 months of the pre-ESRD transition period ('prelude period') with all-cause, cardiovascular and infection-related mortality following dialysis initiation, using Cox (for all-cause mortality) and competing risk (for cause-specific mortality) regressions adjusted for demographics, comorbidities, medications, estimated glomerular filtration rate and serum albumin levels over the 6-month prelude period, and vascular access type at dialysis initiation. During a median follow-up of 2.0 (interquartile range, 1.1-3.2) years following dialysis initiation, a total of 9196 all-cause deaths occurred. Higher ALP levels were incrementally associated with higher all-cause, cardiovascular and infection-related mortality. Compared with patients in the lowest ALP quartile (<66.0 U/L), those in the highest quartile (≥111.1 U/L) had multivariable-adjusted hazard/subhazard ratios (95% confidence interval) of 1.42 (1.34-1.51), 1.43 (1.09-1.88) and 1.39 (1.09-1.78) for all-cause, cardiovascular and infection-related mortality, respectively. The associations remained consistent in various subgroups and after further adjustment for liver enzymes, serum phosphorus and intact parathyroid hormone levels. Higher pre-ESRD serum ALP levels are independently associated with higher post-ESRD mortality risk. Further studies are warranted to determine if interventions that lower pre-ESRD ALP levels reduce mortality in incident dialysis patients.

Association between vascular access creation and deceleration of estimated glomerular filtration rate decline in late-stage chronic kidney disease patients transitioning to end-stage renal disease.

Prior studies have suggested that arteriovenous fistula (AVF) or graft (AVG) creation may be associated with slowing of estimated glomerular filtration rate (eGFR) decline. It is unclear if this is attributable to the physiological benefits of a mature access on systemic circulation versus confounding factors. We examined a nationwide cohort of 3026 US veterans with advanced chronic kidney disease (CKD) transitioning to dialysis between 2007 and 2011 who had a pre-dialysis AVF/AVG and had at least three outpatient eGFR measurements both before and after AVF/AVG creation. Slopes of eGFR were estimated using mixed-effects models adjusted for fixed and time-dependent confounders, and compared separately for the pre- and post-AVF/AVG period overall and in patients stratified by AVF/AVG maturation. In all, 3514 patients without AVF/AVG who started dialysis with a catheter served as comparators, using an arbitrary 6-month index date before dialysis initiation to assess change in eGFR slopes. Of the 3026 patients with AVF/AVG (mean age 67 years, 98% male, 75% diabetic), 71% had a mature AVF/AVG at dialysis initiation. eGFR decline accelerated in the last 6 months prior to dialysis in patients with a catheter (median, from -6.0 to -16.3 mL/min/1.73 m2/year, P < 0.001), while a significant deceleration of eGFR decline was seen after vascular access creation in those with AVF/AVG (median, from -5.6 to -4.1 mL/min/1.73 m2/year, P < 0.001). Findings were independent of AVF/AVG maturation status and were robust in adjusted models. The creation of pre-dialysis AVF/AVG appears to be associated with eGFR slope deceleration and, consequently, may delay the onset of dialysis initiation in advanced CKD patients.

Association Between Vascular Access Creation and Deceleration of Estimated Glomerular Filtration Rate Decline in Late-Stage Chronic Kidney Disease Patients Transitioning to End-Stage Renal Disease

Association Between Vascular Access Creation and Deceleration of Estimated Glomerular Filtration Rate Decline in Late-Stage Chronic Kidney Disease Patients Transitioning to End-Stage Renal Disease

Soy-based renoprotection.

Chronic kidney disease (CKD) is a significant public health problem as risk factors such as advanced age, obesity, hypertension and diabetes rise in the global population. Currently there are no effective pharmacologic treatments for this disease. The role of diet is important for slowing the progression of CKD and managing symptoms in later stages of renal insufficiency. While low protein diets are generally recommended, maintaining adequate levels of intake is critical for health. There is an increasing appreciation that the source of protein may also be important. Soybean protein has been the most extensively studied plant-based protein in subjects with kidney disease and has demonstrated renal protective properties in a number of clinical studies. Soy protein consumption has been shown to slow the decline in estimated glomerular filtration rate and significantly improve proteinuria in diabetic and non-diabetic patients with nephropathy. Soy's beneficial effects on renal function may also result from its impact on certain physiological risk factors for CKD such as dyslipidemia, hypertension and hyperglycemia. Soy intake is also associated with improvements in antioxidant status and systemic inflammation in early and late stage CKD patients. Studies conducted in animal models have helped to identify the underlying molecular mechanisms that may play a role in the positive effects of soy protein on renal parameters in polycystic kidney disease, metabolically-induced kidney dysfunction and age-associated progressive nephropathy. Despite the established relationship between soy and renoprotection, further studies are needed for a clear understanding of the role of the cellular and molecular target(s) of soy protein in maintaining renal function.

Oral adsorbent AST-120 potentiates the effect of erythropoietin-stimulating agents on Stage 5 chronic kidney disease patients: a randomized crossover study

Indoxyl sulfate (IS) suppresses erythropoietin (EPO) activity and exerts renal damage. The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties; however, its roles in the treatment of anemia remain unclear in chronic kidney disease (CKD) patients. Fifty-one Stage 5 predialysis CKD patients with hemoglobin <10 g/dL were randomly assigned to receive two period treatments with AST-120 plus once-monthly administration of continuous EPO receptor activator (CERA, A) and CERA alone (B), with a 4-week washout period in between. Mean changes of serum creatinine, estimated glomerular filtration rate (eGFR) and hemoglobin levels from the baseline were compared between two treatments. The baseline and postintervention mean creatinine levels were 5.48 and 5.36 mg/dL in the Treatment A, and 5.14 mg/dL and 5.61 g/dL in the Treatment B group, respectively (treatment effect P = 0.025, period effect P = 0.467, carryover effect P = 0.384). The baseline and postintervention mean hemoglobin levels were 9.27 and 10.47 g/dL in the Treatment A, and 9.63 g/dL and 9.54 g/dL in the Treatment B group, respectively (treatment effect P = 0.039, period effect P = 0.001, carryover effect P = 0.060). Use of AST-120 significantly reduced IS and p-cresyl sulfate (PCS) levels. Hierarchical regression showed that eGFR was an independent predictor for hemoglobin after adjustment of serum free IS and PCS levels (B = 0.049, P = 0.005). Use of adjuvant AST-120 may improve renal function and hemoglobin levels than use of CERA alone in late-stage CKD patients. The change of eGFR might play an intermediate role between serum IS/PCS and improve hemoglobin levels. The finding offered insight into novel therapeutic strategies of anemia for late-stage CKD patients.

Factors associated with chronic musculoskeletal pain in patients with chronic kidney disease

BackgroundChronic musculoskeletal (MS) pain is common in patients with chronic kidney disease (CKD) undergoing haemodialysis. However, epidemiological data for chronic MS pain and factors associated with chronic MS pain in patients with early- or late-stage CKD who are not undergoing dialysis are limited.MethodA cross-sectional study to evaluate the prevalence of chronic MS pain and factors associated with chronic MS pain in patients with early- and late-stage CKD who were not undergoing dialysis, was conducted. In addition, the distribution of pain severity among patients with different stages of CKD was evaluated.ResultsOf the 456 CKD patients studied, 53.3% (n = 243/456) had chronic MS pain. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, as well as with the calcium × phosphate product levels. In CKD patients with hyperuricemia, chronic MS pain showed a negative, independent significant association with diabetes mellitus as a co-morbidity (odds ratio: 0.413, p = 0.020). However, in the CKD patients without hyperuricemia as a co-morbidity, chronic MS pain showed an independent significant association with the calcium × phosphate product levels (odds ratio: 1.093, p = 0.027). Furthermore, stage-5 CKD patients seemed to experience more severe chronic MS pain than patients with other stages of CKD.ConclusionChronic MS pain is common in CKD patients. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, and with the calcium × phosphate product levels in early- and late-stage CKD patients who were not on dialysis.

Factors related to nephrotic-range proteinuria in late-stage chronic kidney disease patients with diabetes mellitus

Diabetic nephropathy and proteinuria are important risk factors for both end-stage renal disease and cardiovascular events. The present study aimed to identify the factors associated with nephrotic-range proteinuria in patients with advanced diabetic nephropathy. This cross-sectional study enrolled 386 diabetic patients with chronic kidney disease (CKD) stages 3-5, from our outpatient Department of Nephrology. Urinary protein-to-creatinine ratio was recorded. Additionally, other laboratory parameters, body mass index, blood pressure, comorbidities, and medications were also reviewed. The mean age of the patients was 65.1 ± 11.6 years. Among patients with CKD stage 3 and 4, the odds ratio (OR) for nephrotic-range proteinuria in relation with systolic blood pressure significantly increased starting from 121 mmHg (OR 7.04 and 11.79 for systolic blood pressure of 121-140 and ≥141 mmHg, respectively, in comparison with systolic blood pressure below 121 mmHg). In addition, serum phosphorus ≥4.7 mg/dl was associated with significantly higher risk (OR 15.45) for severe proteinuria, compared with a phosphorus level ≤2.6 mg/dl. Finally, hypertriglyceridemia ≥241 mg/dl was also associated with higher OR for severe proteinuria, compared with a triglyceride level ≤200 mg/dl. Similar associations were found in patients with CKD stage 5. Higher systolic blood pressure, serum phosphorus, and triglyceride levels are associated with nephrotic-range proteinuria in patients with diabetic nephropathy and CKD stage 3-5. Further studies should clarify whether a reduction in serum phosphorus would lead to a decrease in proteinuria in these patients.

Changes in levels of copper, iron, zinc, and selenium in patients at different stages of chronic kidney disease

Chronic kidney disease (CKD) is a prevalent disease in the elderly population. Oxidative stress plays an important role in the progression of adverse complications in CKD patients, and many trace elements are involved in the oxidant–antioxidant balance. We investigated serum levels of copper, iron, zinc, and selenium in 145 patients at Stages 1–4 of CKD. There were no significant differences in the copper, iron, and selenium levels between the four stages of CKD. However, the levels of serum zinc showed a statistically decreasing trend in the advanced stages of CKD subjects (p = 0.005). Zinc deficiency may increase oxidative stress and atherosclerotic complications, especially in late-stage CKD patients.

Clinical significance of saliva urea, creatinine, and uric acid levels in patients with chronic kidney disease

To explore the changes and clinical significance of saliva urea, creatinine (Cr), uric acid (UA) in both healthy people and chronic kidney disease (CKD) patients, and to provide a noninvasive, quick, accurate and reliable test to diagnose kindey disease. Urea, Cr and UA in the saliva and serum collected from both healthy people and the CKD patients were measured by biochemical analyzer. We calculated the correlation coefficient of Urea, Cr and UA between the saliva and serum, compared the levels of saliva Urea, Cr and UA among CKD patients in different periods, drew the receiver operation characteristic (ROC) curve and analyzed the sensitivity and specificity of saliva Urea, Cr and UA to predict CKD patients in various periods. The concentrations of Urea, Cr and UA in both the saliva and the serum were positively correlated in healthy individuals and CKD patients (r = 0.918, 0.932, 0.840 and 0.984, 0.971, 0.920). The levels of saliva Urea, Cr and UA in the CKD patients were significantly higher than those of healthy people (P<0.05). Saliva Urea, Cr and UA concentrations of middle and late stage CKD patients were obviously higher than those of healthy people and early stage CKD patients (P<0.05). Areas under the curve (AUC) of the ROC of Urea, Cr and UA to diagnose diverse periods of CKD were 0.898, 0.897 and 0.848. The sensitivity was 0.806, 0.776 and 0.704; and the specificity was 0.968, 0.989 and 0.871. The levels of Urea, Cr and UA between the saliva and the serum are closely related. The concentration of saliva Urea, Cr and UA can reflect the renal damage, monitor kidney function of the CKD patients, and help diagnose middle to late stage CKD patients. It is a simple, nonivasive and quick method.

Long-term renal outcomes of episodic urinary tract infection in diabetic patients

ObjectiveUrinary tract infection (UTI) exists in 9%–20% of female and 3%–11% of male patients with diabetes. Diabetic patients experience increased risk of bacteremia, hospitalization, and mortality; however, few studies report long-term renal outcomes of episodic UTI in diabetic patients with chronic kidney disease (CKD). Research Design and MethodsWe investigated 225 diabetic patients admitted with UTI from 2001 to 2011. Based on the glomerular filtration rate (GFR) on admission, we divided the patients into early- (GFR ≥30ml/min; n=131) and late-stage (stages 4 and 5, GFR <30ml/min; n=94) CKD groups. We compared admission risk factors, post-UTI GFR decline and its long term trend between these groups. ResultsPoor glycemic control contributed to admission with UTI in the early- and late-stage CKD patients (glycosylated hemoglobin: (9.7±2.8% versus 8.6±2.6%). Early-stage CKD patients exhibited higher urinary glucose. Besides, acute kidney injury (AKI) occurred on admission in late-stage CKD patients (mean eGFR 14.2ml/min). However, if the infection was cured, almost all diabetic patients reverted to their GFR trends 6months later. ConclusionsLate-stage CKD diabetic patients with UTI are at increased risk of superimposed AKI. Almost all patients gradually reverted to their GFR trend later after infection was cured. Early recognition of complicating AKI factors and aggressive treatment of symptomatic UTI instead of antibiotic prophylaxis for asymptomatic bacteriuria are suggested.