Early-stage Chronic Kidney Disease Patients Research Articles

Effect of Tyrosine Kinase Inhibitor Therapy on Estimated Glomerular Filtration Rate in Patients with Chronic Myeloid Leukemia

IntroductionThe advent of tyrosine kinase inhibitors (TKIs) was revolutionary in the management of chronic myeloid leukemia (CML). Although TKIs were generally considered to be safe, they can be associated with renal injury. We evaluated the effect of TKIs on renal functions in a cohort of patients with long-term follow-up. Material and MethodsWe retrospectively examined patients with chronic phase CML treated with TKIs. We analyzed the estimated glomerular filtration rate (eGFR) of patients from the initiation of TKI to the last follow-up. eGFR values of CML patients were compared to those of patients with stage 1 or 2 chronic kidney disease (CKD). ResultsA total of 195 patients with CML and 138 patients with CKD were examined. eGFR decline was 1.556 ml/min/1.73m2/year for patients with CML (P = .221). Patients receiving second-generation TKIs (2GTKI) were estimated to have 0.583 ml/min/1.73m2 higher eGFR value than that of the imatinib group, but it was not significant (P = .871). eGFR of patients who had used bosutinib had a downward trend. Duration of TKI therapy, age, and hypertension were found to be significant factors in eGFR decline for CML patients. Lower baseline GFR was associated with an increased risk of CKD development. ConclusionImatinib could result in a decline in eGFR which was clinically similar to early-stage CKD patients. We did not observe significant kidney function deterioration in patients receiving 2GTKIs including dasatinib and nilotinib. We recommend close renal function monitoring in patients receiving imatinib, especially for elderly patients with lower baseline eGFR and hypertension.

Wireless Detection of Trace Ammonia: A Chronic Kidney Disease Biomarker.

Elevated levels of ammonia in breath can be linked to medical complications, such as chronic kidney disease (CKD), that disturb the urea balance in the body. However, early stage CKD is usually asymptomatic, and mass screening is hindered by high instrumentation and operation requirements and accessible and reliable detection methods for CKD biomarkers, such as trace ammonia in breath. Enabling methods would have significance in population screening for early stage CKD patients. We herein report a method to effectively immobilize transition metal selectors in close proximity to a single-walled carbon nanotube (SWCNT) surface using pentiptycene polymers containing metal-chelating backbone structures. The robust and modular nature of the pentiptycene metallopolymer/SWCNT complexes creates a platform that accelerates sensor discovery and optimization. Using these methods, we have identified sensitive, selective, and robust copper-based chemiresistive ammonia sensors that display low parts per billion detection limits. We have added these hybrid materials to the resonant radio frequency circuits of commercial near-field communication (NFC) tags to achieve robust wireless detection of ammonia at physiologically relevant levels. The integrated devices offer a noninvasive and cost-effective approach for early detection and monitoring of CKD.

LncRNA FAS-AS1 served as a diagnostic biomarker of end-stage renal disease and mediated vascular calcification via regulating oxidative stress and inflammation

PurposeVascular calcification is a frequently occurring complication of end-stage renal disease (ESRD). This study focused on the significance of long non-coding RNA Fas cell surface death receptor-antisense 1(lncRNA FAS-AS1) in ESRD-related vascular calcification aiming to explore a potential biomarker for the detection. MethodsThe study enrolled 65 healthy individuals, 79 ESRD patients (48 patients with vascular calcification), and 93 early-stage (I-IV) chronic kidney disease (CKD) patients. The expression of FAS-AS1 in serum was evaluated by real-time quantitative polymerase chain reaction (PCR). The diagnostic potential of FAS-AS1 was assessed in discriminating ESRD patients, vascular calcification, and the severity of vascular calcification. In vitro, the vascular smooth muscle cells (VSMCs) were treated with a hyperphosphatemia medium to evaluate the effect of FAS-AS1 on VSMCs calcification. ResultsElevated serum FAS-AS1 was observed in ESRD patients, which could discriminate from healthy individuals and early-stage CKD patients. FAS-AS1 was associated with the development of ESRD and the occurrence of vascular calcification. FAS-AS1 was also upregulated in vascular calcification patients, especially the patients with severe calcification, which showed diagnostic significance in evaluating vascular calcification degrees. Calcified VSMCs showed significantly increased levels of Ca2+, reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), which was attenuated by silencing FAS-AS1. ConclusionsFAS-AS1 discriminated ERSD patients and was associated with the occurrence of vascular calcification. The knockdown of FAS-AS1 suppressed hyperphosphatemia-induced vascular calcification via alleviating oxidative stress and inflammation.

Elevated Uric Acid Levels with Early Chronic Kidney Disease as an Indicator of New-Onset Ischemic Heart Disease: A Cohort of Koreans without Diabetes.

Several studies have showed that hyperuricemia is related to the development of ischemic heart disease (IHD). There is also growing evidence indicating that hyperuricemia may contribute to the progression of IHD as a pathogenic factor. Ironically, uric acid can be an antioxidant agent, as shown in experimental studies. The aim of our study is to analyse the association between uric acid and IHD with early-stage chronic kidney disease (CKD). Data were assessed from 17,492 participants without cardiovascular disease from the Korean Genome and Epidemiology Study (KoGES) and Korea Health Insurance Review and Assessment (HIRA) data. The subjects were categorized as four groups according to CKD and uric acid levels. We retrospectively evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD by using multivariate Cox regression analysis over a 4-year period from the baseline survey. During the follow-up, 335 individuals (3.4%; 236 men and 99 women) developed IHD. Compared to the participants without elevated uric acid and early CKD HRs for incident IHD according to uric acid levels and early CKD, the uric acid level was 1.13 (95% CI, 0.86-1.48) in participants with elevated uric acid and without early CKD, 0.99 (95% CI, 0.55-1.77) in participants without elevated uric acid and with early CKD, and 1.65 (95% CI, 1.03-2.66) in participants with elevated uric acid and early CKD after adjusting for confounding metabolic factors. Early CKD and high uric acid levels increased the risk of new-onset IHD (HR, 1.65; 95% CI, 1.03-2.66). Elevated uric acid levels were related to an increased risk of incident IHD in early-stage CKD patients. It is expected that uric acid can be a reliable predictor for IHD, even in early-stage CKD patients; thus, in those with CKD, proactively managing uric acid levels can play a significant role in reducing the risk of cardiovascular disease.

Slight Changes in the Gut Microbiome in Early-stage Chronic Kidney Disease of Unknown Etiology.

Gut dysbiosis and changes in short-chain fatty acids (SCFAs) occur in end-stage chronic kidney disease (CKD); however, the degree of these changes in the gut microbiome and serum SCFA profiles in the early stages of CKD,‍ ‍particularly in‍ ‍CKD‍ ‍of unknown etiology (CKDu), is unclear. We herein investigated the gut microbiome and SCFA profiles of early-stage CKD patients (CKD stages 1-3) in a community in Khon Kaen Province, Thailand. Seventy-two parasite-free participants were distributed among a healthy control group (HC, n=18) and three patient groups (an underlying disease group [UD, n=18], early-stage CKD with underlying disease [CKD-UD, n=18], and early-stage CKD of unknown etiology, [CKDu, n=18]). Fecal DNA was individually extracted and pooled for groups of six individuals (three pools in each group) to examine the composition of the gut microbiome using next-generation sequencing. A SCFA ana-lysis was performed on serum samples from each individual using gas chromatography-mass spectrometry. The results revealed that microbial abundance differed between the healthy group and all patient groups (UD, CKD-UD, and CKDu). [Eubacterium]_coprostanoligenes_group was more abundant in the CKDu group than in the HC and CKD-UD groups. Furthermore, serum concentrations of acetate, a major SCFA component, were significantly lower in all patient groups than in the HC group. The present results indicate that minor changes in the gut microbiome and a significant decrease in serum acetate concentrations occur in early-stage CKDu, which may be important for the development of prevention strategies for CKD patients.

Obstacles to Early Diagnosis and Treatment of Pruritus in Patients with Chronic Kidney Disease: Current Perspectives.

Chronic kidney disease-associated pruritus (CKD-aP) is a common condition amongst patients with advanced chronic kidney disease (CKD). Several studies have confirmed that more than four out of ten early-stage CKD patients suffer from this condition, while its prevalence among CKD patients on dialysis reaches up to seven out of ten. It is noted to be associated with other disabling symptoms and serious outcomes. It has significant impact on sleep, mood, daily activities, and quality of life of CKD patients, and increased mortality risk of patients on hemodialysis. The Dialysis Outcomes and Practice Patterns Study found 17% higher mortality among patients with moderate to extreme pruritus compared with patients with no or mild pruritus. Despite its high prevalence, ill-effect, and suffering associated with it, CKD-aP remains surprisingly under-reported on the patient's part and under-recognized by the healthcare team. Even upon being noticed, it remains unattended and poorly treated. Its etiopathogenesis is complex and not fully understood. Many treatment options are available but good quality evidence about most of those is absent, and to date, only two medications are approved for use in this condition. While a validated guideline is very much required for the benefit of the patients and caretakers, further research on several aspects of this issue is required.

Abstract 10491: Drug-Coated Balloon and Drug-Eluting Stent Safety in Patients With Femoropopliteal and Severe Chronic Kidney Disease

Background: Severe-stage chronic kidney disease (CKD) patients were excluded from femoropopliteal disease trials evaluating drug-coated balloons (DCB) and drug-eluting stents (DES) vs. plain balloon angioplasty (POBA) and bare metal stents (BMS). We examined the interaction between CKD status and device type for the association with 24-month all-cause mortality and major amputation risk. Methods: We studied patients undergoing femoropopliteal interventions (9/2016-12/2018) from Medicare-linked VQI registry data. We compared outcomes for: (1) early-stage CKD (stages 1-3) receiving DCB/DES, (2) early-stage CKD receiving POBA/BMS, (3) severe-stage (4-5) CKD receiving DCB/DES, (4) severe-stage CKD receiving POBA/BMS. Results: We studied 8,799 patients (early-stage CKD: 94%; severe-stage: 6%). DCB/DES use was 57% vs. 51% in early-stage vs. severe-stage CKD patients. Twenty-four-month mortality risk for early-stage CKD patients receiving DCB/DES (reference group) was 21% vs. 28% (HR=1.47, 95% CI, 1.31-1.65) for those receiving POBA/BMS; severe-stage CKD patients: those receiving DCB/DES had a 49% (HR=2.61,95% CI, 2.06-3.31) mortality risk vs. 52% (HR=3.64, 95% CI, 2.91-4.55) for those receiving POBA/BMS (interaction P<0.001) ( Figure ). Adjusted analyses attenuated these results. For severe-stage CKD, DCB/DES vs. POBA/BMS mortality risk was not significant at 24 months (post hoc comparison P=0.06) but was higher for POBA/BMS group at 18 months (post hoc P<0.05). Early-stage CKD patients receiving DCB/DES had the lowest 24-month amputation risk (6%), followed by 11% for early-stage CKD-POBA/BMS, 15% for severe-stage CKD-DCB/DES, 16% for severe-stage CKD-POBA/BMS (interaction P<0.001). DCB/DES vs. POBA/BMS amputation rates in severe-stage CKD patients did not differ (post hoc P=0.820). Conclusion: DCB/DES vs. POBA/BMS use severe-stage CKD patients was associated with lower mortality and no difference in amputation outcomes.

Hematological Abnormalities and Comorbidities Are Associated With the Severity of Kidney Disease: A Hospital-Based Cross-Sectional Study in Bangladesh.

Background:Abnormalities in hematology and comorbidities might have a role in chronic kidney disease (CKD) patients. However, the exact relationships between hematological parameters and the severity of CKD are not well understood. Also, the underlying mechanisms remain under investigation. The present study aimed to evaluate the association of different blood parameters and comorbidities among hospitalized CKD patients in Bangladesh.Methods:The present study enrolled admitted CKD patients at Evercare Hospital Ltd, Dhaka, Bangladesh, from January 1, 2021, to August 1, 2021. For this study, the demographic and clinical information of the patients were collected. Then some routine blood tests for the hematological profile of CKD patients were performed. Finally, several statistical methods were performed and data interpretations were done to evaluate the role of hematological changes on CKD patients.Results:Among 300 patients, early-stage CKD patients (ESCKDP) and advanced-stage CKD patients (ASCKDP) were 153 and 147, respectively. The decreased levels of hemoglobin (Hb) and red blood cell (RBC) in ASCKDP were observed. However, the present study found increased levels of corpuscular Hb in ASCKDP than ESCKDP. Also, the present study noticed correlations between these changes and the severity of CKD. Also, we observed a significant difference in age and body mass index between ESCKDP and ASCKDP.Conclusions:Based on our results, lower Hb and RBC levels may use in assessing the severity and the treatment decisions of CKD patients in the hospital setting. Therefore, our findings may assist with developing a treatment protocol for hospitalized CKD patients.

Vascular Calcification in Patients with Early-Stage Chronic Kidney Disease: The Pivotal Role of Estimated Glomerular Filtration Rate

Background: Vascular calcification in advanced chronic kidney disease (CKD) is correlated with uremic toxins and severely impaired calciumphosphate- parathyroid metabolism. The association factors of vascular calcification in early-stage CKD are still unestablished. Objective: To identify the risk factors for vascular calcification in the early-stage CKD, which was the non-target population, different from other previous studies that explored this association in advanced stage CKD. Materials and Methods: The present study was a longitudinal study conducted to examine the risk factors of vascular calcification in CKD stage G2 and G3 patients who had no previous cardiovascular diseases. All parameters including coronary artery calcification (CAC) and abdominal aortic calcification (AAC) at baseline and after twelve months were evaluated. Results: Twenty-two patients without established cardiovascular diseases were included and completed the follow-up period. Mean baseline LDL was 99 mg/dL and no patient received statin. At 12-month, the median CAC score was significantly increased to 266 (126 to 956) versus 282 (198 to 846), (p=0.024]. By multivariable analysis in generalized estimating equations, only estimated glomerular filtration rate (eGFR) was associated with CAC score greater than 400 (aOR 0.92, p=0.041), and AAC score greater than 5 (aOR 0.90, p=0.023). Conclusion: In early-stage CKD, eGFR was associated with vascular calcification. Further studies should explore the potential benefits of delaying CKD progression on vascular calcification in the early-stage CKD patients. Keywords: Chronic kidney disease; Vascular calcification; Coronary artery calcification; Abdominal aortic calcification; Glomerular filtration rate; Renal function

Melamine exposure threshold in early chronic kidney disease patients - A benchmark dose approach.

Environmental melamine exposure has been associated with deteriorating kidney function in early-stage chronic kidney disease patients. In this study, a benchmark dose (BMD) approach was used to establish melamine exposure threshold in 293 patients with eGFR≥30ml/min per 1.73m2. The patients were enrolled 2006-2010 and followed-up for a median of 7.0years to monitor kidney outcomes. Average daily intakes (AvDI) of melamine were estimated using one-spot urine samples collected at enrollment. BMDs and corresponding one-sided 95% lower bound (BMDLs) were derived using established dose-response models relating estimated AvDIs and dichotomous kidney outcomes: doubling of serum creatine levels, eGFRdecreased >3ml/min per 1.73m2 per year, and >30% decline in eGFR during the first 2years. In addition, survival time to doubling of serum creatinine and eGFR decline over time were assessed as continuous endpoints. Given a benchmark response of 0.10, BMDLs ranged from 0.74 to 2.03 μg/kg_bw/day after Bayesian model averaging, a range one to two orders lower than the current WHO recommended tolerable daily intake of 200 μg/kg_bw/day and the US FDA's 63 μg/kg_bw/day. Our results suggest that early-stage CKD patients should strictly refrain from using melamine tableware and related melamine-made products.

Intestinal flora alterations in patients with early chronic kidney disease: a case-control study among the Han population in southwestern China.

ObjectiveIn this case–control study, we retrospectively analyzed the intestinal flora compositions of patients with early-stage chronic kidney disease (CKD).MethodsForty-seven patients with early CKD who were treated at the Traditional Chinese Medicine Hospital between March and October 2018 were enrolled, and 150 healthy volunteers were enrolled in the healthy control group. Fresh stool samples were collected. The V3–V4 region of the bacterial 16S rRNA was amplified via PCR. Biterminal sequencing was performed using the Illumina MiSeq platform. The flora compositions were compared between the two groups.ResultsThe Chao1 and Shannon indices showed significantly lower intestinal flora diversity and abundances in the CKD group than in the healthy controls. Beta diversity analysis revealed notable differences in the intestinal flora compositions between the groups. At the phylum level, Actinobacteria and Proteobacteria abundances were significantly higher in the CKD group. Thirty-one species differed significantly between both groups, among which, differences in Ruminococcus and Roseburia displayed the highest diagnostic values for distinguishing CKD patients from healthy controls.ConclusionsIntestinal flora compositions are altered in early-stage CKD patients among the Han population in southwestern China.

Prevalence of sleep apnoea in non-dialysis chronic kidney disease patients: A systematic review and meta-analysis.

The prevalence of sleep apnoea (SA) in chronic kidney disease (CKD) varies greatly across preceding studies. The aim of our study was to provide a summary of the prevalence of SA among non-dialysis CKD patients. Medline, Embase, Web of Science, China Knowledge Resource Integrated Database, VIP Chinese scientific journal database (VIP) and Wanfang Digital Periodical Full-text database were searched up to September 2018 to identify publications related to the prevalence of SA in non-dialysis CKD patients assessed by sleep questionnaires or sleep respiration monitoring. Random-effects meta-analysis was used to estimate pooled prevalence of SA. And subgroup analysis and meta-regression were conducted as well. The pooled prevalence of SA in the included 26 studies was 38% (95% confidence interval [CI], 21-70%). In subgroup analyses, the pooled prevalence of SA varied using different diagnostic tools. The pooled prevalence of questionnaire-based SA for CKD was 10% (95% CI, 3-27%), while the prevalence of sleep monitoring-based SA was 56% (95% CI, 49-66%). Also, advanced CKD patients had a greater chance to suffer from moderate-to-severe SA than early stage CKD patients. Male patients were more likely to be affected by moderate-to-severe SA than female patients (47% vs 30%, P = 0.018). Sleep apnoea is commonly seen in both early and advanced non-dialysis CKD patients. Sleep related scales provided lower prevalence than instrumental sleep monitoring, therefore, underestimated the presence of SA. The prevalence of SA increases in advanced CKD. And male patients are more likely to be affected by SA than female patients.

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.

Uremic Toxins Affect the Imbalance of Redox State and Overexpression of Prolyl Hydroxylase 2 in Human Adipose Tissue-Derived Mesenchymal Stem Cells Involved in Wound Healing.

Chronic kidney disease (CKD) results in a delay in wound healing because of its complications such as uremia, anemia, and fluid overload. Mesenchymal stem cells (MSCs) are considered to be a candidate for wound healing because of the ability to recruit many types of cells. However, it is still unclear whether the CKD-adipose tissue-derived MSCs (CKD-AT-MSCs) have the same function in wound healing as healthy donor-derived normal AT-MSCs (nAT-MSCs). In this study, we found that uremic toxins induced elevated reactive oxygen species (ROS) expression in nAT-MSCs, resulting in the reduced expression of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions. Consistent with the uremic-treated AT-MSCs, there was a definite imbalance of redox state and high expression of ROS in CKD-AT-MSCs isolated from early-stage CKD patients. In addition, a transplantation study clearly revealed that nAT-MSCs promoted the recruitment of inflammatory cells and recovery from ischemia in the mouse flap model, whereas CKD-AT-MSCs had defective functions and the wound healing process was delayed. Of note, the expression of prolyl hydroxylase domain 2 (PHD2) is selectively increased in CKD-AT-MSCs and its inhibition can restore the expression of HIF-1α and the wound healing function of CKD-AT-MSCs. These results indicate that more studies about the functions of MSCs from CKD patients are required before they can be applied in the clinical setting.

A Pilot Study to Examine the Effects of an Anti-inflammatory Supplement on Eicosanoid Derivatives in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is a progressive disease with an inverse relationship between kidney function and levels of inflammation and oxidative stress. Curcumin and Boswellia serrata have been reported to exert anti-inflammatory effects on the cyclooxygenase and lipoxygenase pathways. Therefore, the purpose of this study was to study the effects of a supplement containing curcumin and B. serrata on eicosanoid derivatives in early stage CKD patients who had not initiated hemodialysis. Sixteen patients with stage 2 and stage 3 CKD (56.0 ± 16.0 years, 171.4 ± 11.9 cm, 99.3 ± 20.2 kg) were randomized into a treatment group with curcumin and B. serrata or a placebo group. The dependent variables prostaglandin E2 (PGE2), 5-hydroxyicosatetraenoic acid, 12-hydroxyicosatetraenoic acid, 15-hydroxyicosatetraenoic acid, and 13-hydroxyoctadecadienoic acid were measured both before and after 8 weeks of supplementation. Results were analyzed by using a repeated-measures analysis of covariance for compliance and body-mass index. A significant group effect (p = 0.05), and a trend for Group × Time interaction (p = 0.056) were detected for PGE2. No significant differences were observed for any other variables. This is the first article of baseline levels of the dependent variables in early stage CKD, and the first article to show a significant effect of these supplements on PGE2 in early stage CKD. Further studies are needed to determine whether curcumin and B. serrata may be effective means to reduce inflammation in patients with CKD.

Applying the Strategies of Helping Relationship From Significant Others in Patients With Chronic Kidney Disease

The absence of easily perceived symptoms in the early stages of chronic kidney disease (CKD) causes low levels of awareness and treatment of this disease. Therefore, adherence to measures that may prevent disease progression, i.e., lifestyle changes, regular clinic visits, and timely medication administration, is often low among early-stage CKD patients. However, continuous assistance from significant others through trusting, understanding, sharing, and coaching assistance may promote a healthy lifestyle and prevent progression of the disease. The necessary characteristics of significant others include dependability, credibility, and positivity. Significant others may use their understanding, caring, faith, and honesty to help patients face CKD and improve self-care efficacy. This article discusses the assistance that significant others may provide to CKD patients, including warning mechanisms, target setting, encouragement, and feedback. By developing the functions of supervision, companionship, and support, significant others may help patients live a healthier life and improve their medical compliance and thus postpone disease progression.

Keto-supplemented Low Protein Diet: A Valid Therapeutic Approach for Patients with Steroid-resistant Proteinuria during Early-stage Chronic Kidney Disease.

Low protein diets supplemented with keto acid (sLPD) are recommended for patients with stage 3-5 chronic kidney disease (CKD). This study assessed whether sLPD is beneficial for patients with steroid-resistant proteinuria during early-stage CKD. A 1-year randomized controlled trial was conducted from 2010 to 2012. In this study, 108 proteinuric patients who were steroid-resistant were assigned to a sLPD group (0.6 g/kg/d with 0.09 g/kg/d keto acids) or a normal protein diet group (NPD, 1.0 g/kg/d). Estimated dietary protein intake, urinary protein excretion, remission rate, renal function, nutritional status, and blood pressure were measured. Baseline characteristics were comparable between the sLPD group (47 patients) and the NPD group (49 patients). Urinary protein excretion significantly decreased in sLPD compared to NPD in months 6, 9, and 12 (P<0.05). Proteinuria reduction was higher in sLPD than in NPD (P<0.001) at the end of the study. Complete remission and partial remission rates were higher in sLPD than in NPD. Serum albumin and pre-albumin levels were higher in sLPD than in NPD in months 9 and 12 (P<0.05). Serum total cholesterol and triglyceride levels declined more significantly in sLPD than in NPD (P<0.01) at the end of the study. There were no differences in nutritional status, renal function, hemoglobin, or blood pressure between the two groups. sLPD is both nutritionally safe and beneficial, providing nephroprotective effects for early-stage CKD patients with steroid-resistant proteinuria.

Caveolin-1 single-nucleotide polymorphism and arterial stiffness in non-dialysis chronic kidney disease.

Arteriosclerosis is an independent predictor of increased cardiovascular mortality in chronic kidney disease (CKD). Histologically it is characterized by hypertrophy and fibrosis of the arterial media wall leading to increased arterial stiffness and end-organ damage. Caveolin-1 acts as an intracellular signalling pathway chaperone in human fibrotic and vascular diseases. The purpose of this study was to assess the association between caveolin-1 (CAV1) single-nucleotide polymorphism (SNP) rs4730751 and arterial stiffness as measured by arterial pulse wave velocity (PWV) in an early-stage CKD cohort and in a cohort with more severe CKD. Two prospectively maintained patient cohorts with non-dialysis CKD were studied: 144 patients in the Chronic Renal Impairment in Birmingham (CRIB) cohort and 147 patients in the Renal Impairment in Secondary Care (RIISC) cohort, with matched exclusion criteria and DNA sampling availability. At entry to each cohort database, each patient's initial arterial PWV was measured, as well as their anthropomorphic and biochemical data. CAV1 rs4730751 SNP genotyping was performed using Taqman technology. The CAV1 rs4730751 SNP CC genotype was associated with lower arterial PWV in both CRIB early stage CKD patients [8.1 versus 8.6 m/s; coefficient -0.780 (-1.412, -0.149); P = 0.016] and RIISC more advanced stage CKD patients [8.7 versus 9.4 m/s; coefficient -0.695 (-1.288, -0.102); P = 0.022]; these relationships held following adjustment for other important confounders. This replicated study suggests potential utility of the studied CAV1 SNP as a genetic biomarker in CKD and a role for CAV1 in the development of arteriosclerosis in this setting. Further studies are warranted to further explore the basic science driving these clinical observations.

Low ankle-brachial index is associated with early-stage chronic kidney disease in type 2 diabetic patients independent of albuminuria.

AimsThe role of low ankle-brachial index (ABI) in early-stage chronic kidney disease (CKD) is not fully known. This study was designed to investigate the prevalence of low ABI in early-stage CKD defined as an estimated glomerular filtration rate (eGFR) between 60–89 ml/min/1.73 m2 of type 2 diabetic patients without albuminuria and to determine the association between the low ABI and mildly decreased eGFR.MethodsThe cross-sectional study enrolled 448 type 2 diabetic patients with normoalbuminuria. The patients were stratified into two groups according to the CKD-EPI eGFR level: the normal group with eGFR level ≥90 mL/min/1.73 m2 and the lower group with eGFR of 60–89. ABI was categorized as normal (1.0–1.39), low-normal (0.9–0.99), and low (<0.9). Both stepwise forward multiple linear regression and binary logistic regression analyses were performed to examine the association between ABI categories and eGFR levels and to assess the relation of low ABI and early-stage CKD.ResultsThe prevalence of low ABI in early-stage CKD of type 2 diabetic patients without albuminuria was 39.5%. Low ABI was associated with an approximate 3-fold greater risk of early-stage CKD in bivariate logistic regression analysis, and remained significantly associated with a 2.2 fold risk (95% confidence interval: 1.188–4.077; P = 0.012) after adjusting traditional chronic kidney disease risk factors.ConclusionsThere was a high prevalence of low ABI in early-stage CKD patients of type 2 diabetes with normoalbuminuria and a close relation between low ABI and early-stage CKD, suggesting that we should pay much more attention to the patients who have only mildly decreased eGFR and normoalbuminuria but have already had a low ABI in clinic work and consider the preventive therapy in early stage.

Effects of insulin resistance on left ventricular hypertrophy in patients with CKD stage 1-3.

BackgroundLeft ventricular hypertrophy (LVH) existed in patients with early stage chronic kidney disease (CKD). But whether insulin resistance (IR) exists in these patients and has some definite relationship with LVH, is unknown.MethodsHomeostatic model method was used for detecting homeostasis model assessment of insulin resistance (HOMA-IR) in 336 subjects including 286 patients with early stage CKD and 50 control subjects, and HOMA-IR and other clinical data in all subjects were obtained based on standard methods. Then, the relationship between LVH, IR and other relevant clinical data were analyzed.ResultsIR and LVH existed in early stage CKD patients. The prevalence of LVH in patients with IR was significantly higher than those without, and patients with LVH had a higher prevalence of IR than those without. The patients with IR or LVH had lower levels of e-GFR, hemoglobin (Hb) and total cholesterol, while higher levels of blood urea nitrogen (BUN), serum creatinine (Scr), intact parathyroid hormone (iPTH), CRP and systolic blood pressure (SBP). HOMA-IR had positive correlations with left ventricular mass index (LVMI). HOMA-IR and LVMI had positive correlations with BUN, Scr, iPTH and CRP, but negative with e-GFR and Hb. Multiple linear stepwise regression analysis showed that e-GFR, FINS, Hb and SBP enter the regression equation. Binary unconditional logistic regression analysis indicated that the main risk factors for LVH were CKD and IR (P < 0.05, respectively).ConclusionBoth IR and LVH existed in early stage CKD patients and were more severe with the development of CKD. IR had a significant correlation with LVH. Furthermore, decline of e-GFR, hypertension and anemia were also associated with both IR and LVH and may have some effects in the mechanism of IR on the development of LVH.