Stage G3b Research Articles

Prevalence of anemia in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB).

BackgroundThe Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD.MethodsIn total, 31,082 adult outpatients with estimated glomerular filtration rates of 5–60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.ResultsThe mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09–2.58]), G4 (5.50 [4.80–6.31]), and G5 (9.75 [8.13–11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5.ConclusionsWe determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study.

P0218SHEAR WAVE ELASTOGRAPHY AS A NON-INVASIVE MARKER OF RENAL FIBROSIS IN NATIVE DIABETIC KIDNEY DISEASE

Abstract Background and Aims Current assessment of diabetic kidney disease (DKD) is limited to estimated glomerular filtration rate (eGFR) and albuminuria. These are inadequate as DKD often has heterogenous clinical phenotypes. There is need for a marker of intra-renal fibrosis. Native kidney biopsy remains the only reference method in clinical practice for this purpose, but is invasive and impractical for repeated evaluations. Recently, two-dimensional ultrasound shear wave elastography (SWE) has emerged as a non-invasive technique to assess renal parenchymal stiffness with renal fibrosis. We aim to investigate SWE-derived estimates of tissue stiffness with different DKD stages in an Asian population. Method In this cross-sectional pilot study, 58 patients with DKD were recruited from a single centre ambulatory Nephrology clinic. Laboratory values were taken within 1 week of undergoing SWE, with DKD staging by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines and eGFR calculated using the CKD-EPI equation. 13 patients had histological diagnoses of DKD; 2 (15.3%) Stage G1-2; 5 (38.5%) Stage G3; 5 (38.5%) Stage G4 and 1 (7.7%) Stage G5 subjects, with native kidney biopsies performed within 4 months of study recruitment. 2D SWE was performed with a 2-5 MHz transducer on an Axiplorer© ultrasound system (Supersonic Imagine, Paris) by a single Nephrologist blinded to laboratory results. Using a previously described protocol, 6 SWE measurements were taken from the cortical mid-pole of bilateral kidneys, and renal elasticity estimated as Young’s Modulus (YM) in kilopascals (kPa), (Figure 1). Results Study population were 62.1% male (36/58) and 62.1% ethnic Chinese (36/58), with diabetes duration of 11.7 ± 9.2 years. Median eGFR was 35.0 (40-101) mL/min per 1.73 m2, with 6 (10.3%) DKD Stage G1-2; 34 (58.6%) Stage G3; 13 (22.4%) Stage G4 and 5 (8.6%) Stage G5 patients. There were moderate correlations between YM values in bilateral kidneys. Left kidney maximal YM generally increased in accordance with DKD stage (Stage G1-2: 20.6 kPa, Stage G3A: 13.5 kPa, Stage G3B: 22.4 kPa, Stage G4-5: 30.9 kPa, p <0.01). Kidney depth correlated moderately with body mass index (BMI). After controlling kidney depth and BMI, there was a moderately positive correlation between right kidney YM and DKD stage (Maximal YM; r = 0.4, p < 0.01, Mean YM; r = 0.31, p = 0.02). eGFR negatively correlated with bilateral kidney maximal YM (right r = -0.2, p = 0.04, and left r = -0.3, p = 0.03, respectively). Importantly, there was a strong correlation between right kidney mean YM and histological grading of interstitial fibrosis and tubular atrophy (r = 0.9, p = 0.01). There is no correlation between kidney elasticity and percentage of sclerosed glomeruli. Using a cut-off of 13.5 kPa for mean estimated tissue YM, the area under the receiver operator curve was 0.8 to distinguish DKD Stage G1 and G2 from G3A (sensitivity 83.3%, specificity 80.0%). Conclusion SWE-derived estimates of renal stiffness appear to increase with DKD stage. The strong correlation with histological markers of fibrosis indicate that observed differences are due to renal parenchymal stiffness. SWE shows promise as a non-invasive marker of renal fibrosis, although large multi-centre studies are required to validate these findings.

J-CKD-DB: a nationwide multicentre electronic health record-based chronic kidney disease database in Japan

The Japan Chronic Kidney Disease (CKD) Database (J-CKD-DB) is a large-scale, nation-wide registry based on electronic health record (EHR) data from participating university hospitals. Using a standardized exchangeable information storage, the J-CKD-DB succeeded to efficiently collect clinical data of CKD patients across hospitals despite their different EHR systems. CKD was defined as dipstick proteinuria ≥1+ and/or estimated glomerular filtration rate <60 mL/min/1.73 m2 base on both out- and inpatient laboratory data. As an initial analysis, we analyzed 39,121 CKD outpatients (median age was 71 years, 54.7% were men, median eGFR was 51.3 mL/min/1.73 m2) and observed that the number of patients with a CKD stage G1, G2, G3a, G3b, G4 and G5 were 1,001 (2.6%), 2,612 (6.7%), 23,333 (59.6%), 8,357 (21.4%), 2,710 (6.9%) and 1,108 (2.8%), respectively. According to the KDIGO risk classification, there were 30.1% and 25.5% of male and female patients with CKD at very high-risk, respectively. As the information from every clinical encounter from those participating hospitals will be continuously updated with an anonymized patient ID, the J-CKD-DB will be a dynamic registry of Japanese CKD patients by expanding and linking with other existing databases and a platform for a number of cross-sectional and prospective analyses to answer important clinical questions in CKD care.

Reno-protective effects of oral alkalizing agents in chronic kidney disease with aciduria: protocol for a randomized cohort study

BackgroundAciduria caused by urinary excretion of acidic metabolic wastes produced in daily life is known to be augmented in patients with chronic kidney disease (CKD). To evaluate the reno-protective effect of oral alkalizing agents for the improvement of metabolic acidosis and neutralization of intratubular pH in the patients with mild stages of CKD. Also, to identify reno-protective surrogate markers in the serum and urine that can closely associate the effect of urine alkalization.MethodsIn this single-centered, open-labeled, randomized cohort study, patients with CKD stages G2, G3a and G3b, who visited and were treated at Tohoku University Hospital during the enrollment period were registered. We administered sodium bicarbonate or sodium-potassium citrate as the oral alkalinizing agents. A total of 150 patients with CKD will be randomly allocated into the following three groups: sodium bicarbonate, sodium-potassium citrate and standard therapy group without any alkalinizing agents. The data of performance status, venous blood test, spot urine test, venous blood-gas test, electrocardiogram, renal arterial ultrasonography and chest X-ray will be collected at 0, 6, 12 and 24 weeks (short-term study) from starting the interventions. These data will be also collected at 1 and 2 years (long-term study). The samples of plasma and serum and early-morning urine at every visit will be acquired for the analysis of renal function and surrogate uremic biomarkers.The recruitment for this cohort study terminated in March, 2018, and the follow-up period for all the enrolled subjects will be terminated in December, 2020. The primary endpoint will be the development of originally-defined significant renal dysfunction or the occurrence of any cerebrovascular disease in the short-term study. The secondary endpoint will be the same endpoints as in the long-term study, or the patients with significant changes in the suggested the surrogate biomarkers.DiscussionThe findings of this study will address the importance of taking oral alkalizing agents in the patients with early stages of CKD, furthermore they could address any new surrogate biomarkers that can be useful from early stage CKD.Trial registrationRegistered Report Identifier: UMIN000010059 and jRCT021180043.The trial registration number; 150.Date of registration; 2013/02/26.

Influence of chronic kidney disease and haemodialysis on stroke outcome.

Stroke patients with underlying chronic kidney disease (CKD) and those on haemodialysis have complex rehabilitation needs, and their survival and functional outcomes are limited. This study aimed to review post-stroke survival and functional outcomes following rehabilitation in patients with CKD and those on haemodialysis. We conducted a retrospective analysis of consecutive stroke patients with underlying CKD (Stages G3b, G4 and G5; n = 30) and those on dialysis at the time of stroke (n = 7), who underwent in-patient rehabilitation between June 2008 and May 2017. The mean duration of follow-up was 56 months. Demographic details, associated comorbidities and laboratory parameters were reviewed. Baseline and follow-up scores of the National Institute of Health Stroke Scale (NIHSS) and Functional Independence Measure (FIM), and dates of death of the patients were analysed. Of the 37 consecutive stroke patients (mean age 64.7 years), 34 had ischaemic stroke and three had haemorrhagic transformation. Significant improvements in NIHSS and FIM scores were observed from the time of admission to after discharge. Older age, longer duration of hospital stay, lower estimated glomerular filtration rate and low haemoglobin levels were all significantly related to mortality. Despite significant functional and neurological improvements following rehabilitation, stroke patients with underlying CKD had higher average duration of hospital stay, more recurrent hospitalisations and poorer survival outcomes than those without underlying CKD. This could be attributed to the complications associated with CKD rather than stroke. Multidisciplinary community rehabilitation may be an alternative to reduce recurrent hospitalisations and morbidity in this group of patients.

&lt;p&gt;Treatment Costs for Patients with Chronic Kidney Disease Who Received Multidisciplinary Care in a District Hospital in Thailand&lt;/p&gt;

AimTo estimate direct medical treatment costs in patients with pre-dialysis chronic kidney disease (CKD) in a district hospital and to analyze the factors that affected the treatment costs.Patients and MethodsData were retrospectively retrieved from the hospital database in the period from January 2015 to December 2017. Patients who were diagnosed with CKD and had visited ambulatory care services at least two times during the index year (January to December 2015) were included. Patients’ data were excluded if they had cancer, had received renal replacement therapy, or had been referred to receive treatment at other hospitals. Treatment costs based on the providers’ perspectives in the first and second years after the index year were assessed. Descriptive statistics were used to analyze patients’ characteristics, and multiple linear regression was used to analyze the factors in the cost model.ResultsData of 212 patients with CKD stage G3a, G3b, or G4 who met inclusion and exclusion criteria were included for analysis. Average costs for treatment in year 1 and year 2 were not statistically different. Total cost was 5701.34 Thai Baht (THB) per year. The total cost for patients with CKD stage G4 was two times greater than for patients with CKD stage G3. Costs were increased for longer hospitalization, more frequent ambulatory visits, having diabetes mellitus or dyslipidemia as a comorbidity, and uncontrolled fasting blood glucose (FBG). A cost model with R2=0.906 was provided. Significant predictors were length of stay, ambulatory visits, diabetes mellitus, dyslipidemia, serum creatinine, FBG, and body mass index.ConclusionTotal annual treatment costs for the 2 years were not different. A more advanced stage of CKD, having diabetes mellitus or dyslipidemia as comorbidities, and uncontrolled FBG were significantly associated with increased costs for treatment in patients with pre-dialysis CKD.

Medical and Dental Visits of Chronic Kidney Disease-Diagnosed Participants Analyzed From the Specific Health Checkups Results in Japan: TAMA MED Project-CKD.

BackgroundSince 2012, Tama City has promoted the early detection of chronic kidney disease (CKD), through an initiative that measures serum creatinine as part of the specific health checkups. We examined preventive measures against CKD deterioration based on the outcomes of this initiative.MethodsThe complications, medication status, body mass index, smoking status and other determining factors were surveyed among CKD-diagnosed participants over 3 years between 2013 and 2015. Moreover, factors aggravating CKD were investigated via a survey of medical and dental visits based on health insurance claim data over the same period.ResultsThere was an increased rate of comorbid hypertension with each increase in the CKD stage. Comorbidity rates of diabetes mellitus, dyslipidemia, obesity, and smoking increased until CKD stage G4, and then decreased from stage G5. A substantial number of participants with CKD stage G3b and above were not medicated despite comorbidities like hypertension, diabetes mellitus and dyslipidemia. While the rate of regular visits at medical institutions was seen to increase significantly in accordance with the worsening degree of CKD, there were also individuals who, despite having severe CKD, did not visit medical institutions specializing in internal medicine. The rate of dental visits decreased as the CKD stage increased, and further decreased as the diabetic control status worsened.ConclusionsCKD patients should become aware of the importance of the dental visit because only a limited number of patients with advanced CKD received dental care.

A 91-year-old woman with severe aortic stenosis successfully underwent maintenance hemodialysis via arteriovenous fistula after transcatheter aortic valve implantation: a case report with literature review

BackgroundTranscatheter aortic valve implantation (TAVI) has evolved to be a treatment of choice in high-risk patients with aortic stenosis (AS). However, it is not known whether TAVI is safe and beneficial for the creation of arteriovenous fistula for maintenance hemodialysis in high-risk patients with severe AS.Case presentationA 91-year-old woman was referred to our hospital due to oligoanuria and progressive renal dysfunction. She was diagnosed with anti-glomerular basement membrane (GBM) disease. She had hypertension, chronic kidney disease stage G3b, and AS. We chose not to perform immunosuppressive therapy and plasmapheresis for anti-GBM disease because the risk of death outweighed the benefit of treatment. Hemodialysis with a venous catheter was initiated for the renal indication. As she showed severe AS, she had a risk of cardiac decompensation after arteriovenous fistula creation for dialysis. Following the clinical decision-making process, she underwent TAVI. Although she required the implantation of a cardiac pacemaker for an advanced atrioventricular block that occurred 11 days after TAVI, arteriovenous fistula was successfully created thereafter. She could undergo maintenance hemodialysis using arteriovenous fistula.ConclusionsTAVI is safe and beneficial for the creation of arteriovenous fistula shortly after initiating acute hemodialysis using a catheter in a very old patient with anti-GBM disease.

Changes in Serum and Urinary Potassium Handling Associated with Renin-Angiotensin-Aldosterone System Inhibitors in Advanced Chronic Kidney Disease Patients.

ObjectiveThis study aimed to (i) compare the extent of urinary potassium (K+) excretion in addition to the changes in serum K+ concentration: and (ii) clarify the association between changes in serum K+ concentration, urinary K+ excretion, and acid-base status with or without renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with advanced chronic kidney disease (CKD) stages.MethodsSix hundred and ninety-one patients with advanced CKD (CKD G3b, 161; G4, 271; G5, 259) were retrospectively evaluated. Differences in serum K+ concentration, urinary K+ excretion, and serum sodium and chloride differences (Na+−Cl-) were compared among patients with RAAS inhibitors, RAAS inhibitors and diuretic agents, and without either medication in each CKD stage.ResultsSerum K+ concentrations in patients with RAAS inhibitors were significantly higher than in those with RAAS inhibitors and diuretics in CKD stage G3b and the other two treatment groups in CKD stage G4. Urinary K+ excretion among the three groups did not differ significantly in each CKD stage. Serum Na+−Cl- differences in patients with RAAS inhibitors were significantly smaller than in those with RAAS inhibitors and diuretics in CKD stages G3b (p = 0.006) and the other two groups in CKD stage G4 (vs. RAAS inhibitors and diuretics, p <0.001; vs. without either medication, p = 0.008).ConclusionOur study demonstrated that RAAS inhibitor use might be associated with hyperkalemia via not decreased urinary K+ excretion but rather K+ redistribution from intracellular to extracellular fluid induced by the progression of metabolic acidosis in patients with advanced CKD, particularly stages G3b and G4.

14-OR: The Cost of Chronic Kidney Disease Progression in Type 2 Diabetes Patients

This analysis assessed healthcare costs associated with progression of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D). Adults (&amp;lt;85 years old) with T2D and ≥3 eGFR observations were identified in the Optum Clinformatics database (01/2010−09/2017). The first eGFR (index) following T2D diagnosis set the baseline CKD Stage: normal eGFR, Stage G3a, Stage G3b, or Stage G4. Stage G5 patients were excluded. CKD progression was defined by an eGFR indicating higher CKD Stage within 12 months of index and eGFR confirmation &amp;gt;90 days later. Non-progression required an eGFR indicating same stage within 12 months and eGFR confirmation of same stage &amp;gt;12 months post-index. Per-patient per-month (PPPM) healthcare costs evaluated from index to the earliest of end of eligibility or data were compared between progressors and non-progressors by baseline CKD Stage, and adjusted costs were compared using multivariate linear regressions. Of the 204,767 patients selected, 4.8% progressed ≥1 CKD Stage within a year. Progressors were older (72.5 vs. 64.5 years), more likely to be female (55.6% vs. 51.2%) and had a higher Diabetes Complications Severity Index (2.12 vs. 1.17) compared to non-progressors. Healthcare costs PPPM for progressors vs. non-progressors were $2,685 vs. $1,659 for baseline normal eGFR, $3,131 vs. $2,003 for G3a, $5,138 vs. $2,396 for G3b and $14,400 vs. $3,475 for G4. Among patients with confirmed progression status, progressors represented 4.1%, 8.5%, 5.5% and 4.2% of those from normal eGFR, G3a, G3b and G4, respectively. Controlling for baseline characteristics, the adjusted incremental post-index healthcare costs associated with progressors were $674 for baseline normal eGFR, $947 for G3a, $2,625 for G3b, and $10,704 for G4. All comparisons tested at p&amp;lt;0.001. In patients with T2D, CKD progression was associated with increasingly higher incremental healthcare costs at each CKD stage, with the largest increase in cost observed from Stage G4 to Stage G5. Disclosure L. Blonde: Consultant; Self; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi US. Research Support; Self; Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US. J.A. Vassalotti: Advisory Panel; Self; Merck &amp; Co., Inc. Consultant; Self; Janssen Pharmaceuticals, Inc., KPMG. D. Pilon: Other Relationship; Self; Janssen Scientific Affairs, LLC., Novartis Pharmaceuticals Corporation. W. Wynant: Consultant; Self; AbbVie Inc., Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Genentech, Inc., GlaxoSmithKline plc., Janssen Scientific Affairs, LLC., Novartis Pharmaceuticals Corporation, Novartis Pharmaceuticals Corporation, Taiho Pharmaceutical Co., Ltd. M. Zhdanava: Other Relationship; Self; Janssen Scientific Affairs, LLC., Novartis Pharmaceuticals Corporation. P. Lefebvre: Research Support; Self; Janssen Scientific Affairs, LLC. J. Voelker: Consultant; Self; Janssen Scientific Affairs, LLC. R. Bailey: Employee; Self; Janssen Scientific Affairs, LLC. Stock/Shareholder; Self; Johnson &amp; Johnson. M. Durkin: Employee; Self; Janssen Scientific Affairs, LLC. Funding Janssen Scientific Affairs, LLC

Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study.

BackgroundPatients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this population are scarce.MethodsA total of 5217 adults with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 or an eGFR ≥60 mL/min/1.73m2 and overt proteinuria (>500 mg/day) were studied. Self-reported data on current medication use were assessed at baseline (2010–12) and after 4 years of follow-up (FU). Prevalence and risk factors associated with polypharmacy (defined as the regular use of five or more drugs per day) as well as initiation or termination of polypharmacy were evaluated using multivariable logistic regression.ResultsThe prevalence of polypharmacy at baseline and FU was almost 80%, ranging from 62% in patients with CKD Stage G1 to 86% in those with CKD Stage G3b. The median number of different medications taken per day was eight (range 0–27). β-blockers, angiotensin-converting enzyme inhibitors and statins were most frequently used. Increasing CKD G stage, age and body mass index, diabetes mellitus, cardiovascular disease and a history of smoking were significantly associated with both the prevalence of polypharmacy and its maintenance during FU. Diabetes mellitus was also significantly associated with the initiation of polypharmacy [odds ratio (OR) 2.46, (95% confidence interval 1.36–4.45); P = 0.003].ConclusionMedication burden in CKD patients is high. Further research appears warranted to address the implications of polypharmacy, risks of drug interactions and strategies for risk reduction in this vulnerable patient population.

Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients

Several microRNAs (miRNAs) have been linked to chronic kidney disease (CKD) mortality, cardiovascular (CV) complications and kidney disease progression. However, their association with clinical outcomes remains poorly evaluated. We used real-time qPCR to measure serum levels of miR-126 and miR-223 in a large cohort of 601 CKD patients (CKD stage G1 to G5 patients or on renal replacement therapy – CKD G5D) from Ghent University Hospital and 31 healthy controls. All-cause mortality and cardiovascular and renal events were registered as endpoints over a 6 year follow-up period. miR-126 levels were significantly lower from CKD stage G2 on, compared to controls. The serum levels of miR-223 were significantly lower from CKD stage G3B on. When considering overall mortality, patients with levels of either miR-126 or miR-223 below the median had a lower survival rate. Similar results were observed for CV and renal events. The observed link between the two miRNAs’ seric levels and mortality, cardiovascular events or renal events in CKD appears to depend on eGFR. However, this does not preclude their potential role in the pathophysiology of CKD. In conclusion, CKD is associated with a decrease in circulating miR-223 and miR-126 levels.

Interference Rendering Capillary Electrophoresis of Serum Proteins Uninterpretable

The authors report a clinical case where biological interference rendered the electrophoretic trace of serum proteins obtained by capillary electrophoresis as uninterpretable. Electrophoresis of serum proteins and immunotyping immunoassay were performed on Capillary 2 Flex Piercing® Sebia. A 72-year-old male patient was hospitalized in the clinical hematology department for deep lymphadenopathies with hepatocellular failure. The biological assessment revealed chronic renal failure stage G3b, icteric cholestasis with alkaline phosphatase levels, and hepatic cytolysis. Electrophoresis of serum proteins showed a thickening at the base of albumin peak on its anodic slope but, in particular, it revealed the appearance of a super-numerary split peak between albumin and α1 globulins. These peaks made it impossible to identify and integrate peaks. Based on the clinical information, immunotyping immunoassay was performed on the same sample. The comparison of the different curves with the reference curve does not show any monoclonal immunoglobulinopathy but eliminates all the supernumerary peaks. Suspecting an interference, a Hydrasys 2 Scan® agarose gel electrophoresis (Sebia) was run on the same sample; however, it did not show qualitative anomalies interfering with identification and integration of all the peaks. Our clinical case emphasizes the importance of the knowledge of certain endogenous interferences that may be the origin of unusual images when interpreting electrophoretic profiles, especially in capillary electrophoresis.

Association between intensity of statin therapy and mortality in persons with chronic kidney disease.

The 2013 American College of Cardiology/American Heart Association lipid guideline recommends statin dosing based on intensity, rather than targeting specific low-density lipoprotein cholesterol (LDL-C) concentrations, among general populations. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) lipid guideline recommends statins for most adults with chronic kidney disease (CKD), but dose-dependent statin effects in CKD are unclear. We performed a retrospective cohort study of US veterans with CKD Stages G3a, G3b or G4, and new, persistent statin use, from 2005 to 2015. We tested the association of intensity of statin therapy [categorized as low (expected LDL-C reduction <30%), medium (30 to <50%) or high (≥50%)] during the initial 1-year exposure period, with all-cause mortality over the subsequent 4 years. We used Cox proportional hazard models to evaluate the association between statin intensity and all-cause mortality, adjusting for demographics, comorbidities and laboratory measurements. Our cohort included 65 292 persons, of whom 40 124 (61.5%) had CKD G3a, 20 183 (30.9%) G3b and 4985 (7.6%) G4. Overall, 4878 (7.5%) used high-intensity, 39 070 (59.8%) used moderate-intensity and 21 344 (32.7%) used low-intensity statins. High-intensity statins were used more in recent years, and among persons diagnosed with atherosclerotic cardiovascular disease. There was no association between statin intensity and mortality in unadjusted or multivariable-adjusted analyses. There were no significant associations between statin intensity over 1 year of exposure and subsequent mortality among US veterans with CKD. This supports the current KDIGO guideline recommendations to use statins and dosages that have been studied specifically in CKD populations, rather than intensity-based dosing.

Hospital admissions for severe infections in people with chronic kidney disease in relation to renal disease severity and diabetes status.

SummaryBackgroundImmunosuppressive agents are being investigated for the treatment of chronic kidney disease (CKD) but may increase risk of infection. This was a retrospective observational study intended to evaluate the risk of hospitalized infection in patients with CKD, by estimated glomerular filtration rate (eGFR) and proteinuria status, aiming to identify the most appropriate disease stage for immunosuppressive intervention.MethodsRoutine UK primary‐care and linked secondary‐care data were extracted from the Clinical Practice Research Datalink. Patients with a record of CKD were identified and grouped into type 2, type 1 and nondiabetes cohorts. Time‐dependent, Cox proportional hazard models were used to determine the likelihood of hospitalized infection.ResultsWe identified 97 839 patients with a record of CKD, of these 11 719 (12%) had type 2 diabetes. In these latter patients, the adjusted hazard ratios (aHR) were 1.00 (95% CI: 0.80‐1.25), 1.00, 1.03 (95% CI: 0.92‐1.15), 1.36 (95% CI: 0.20‐1.54), 1.82 (95% CI: 1.54‐2.15) and 2.41 (95% CI: 1.60‐3.63) at eGFR stages G1, G2 (reference), G3a, G3b, G4 and G5, respectively; and 1.00, 1.45 (95% CI: 1.29‐1.63) and 1.91 (95% CI: 1.67‐2.20) at proteinuria stages A1 (reference), A2 and A3, respectively. All aHRs (except G1 and G3a) were significant, with similar patterns observed within the non‐DM and overall cohorts.Conclusions eGFR and degree of albuminuria were independent markers of hospitalized infection in both patients with and without diabetes. The same patterns of hazard ratios of eGFR and proteinuria were seen in CKD patients regardless of diabetes status, with the risk of each outcome increasing with a decreasing eGFR and increasing proteinuria. Infection risk increased significantly from eGFR stage G3b and proteinuria stage A2 in type 2 diabetes. Treating type 2 DM patients with CKD at eGFR stages G1‐G3a with immunosuppressive therapy may therefore provide a favourable risk‐benefit ratio (G1‐G3a in type 2 diabetes; G1‐G2 in nondiabetes and overall cohorts) although the degree of proteinuria needs to be considered.

Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction.

The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)-infected patients with renal dysfunction. The study included genotype 2 HCV-infected patients who received SOF and RBV between July 2014 and May 2017. The sustained virologic response (SVR) after the treatment and safety during the therapy were evaluated according to renal function. A total of 231 patients were included in this study. The median age was 62years old, and 45.9% (106/231) were men. Of the 231 patients, 191 (82.8%) and 40 (17.2%) were classified as having chronic kidney disease (CKD) stages G1/2 and G3, respectively. The overall SVR rate was 97% (224/231). The SVR rates in patients with CKD stages G1, 2, G3a, and G3b were 98.1%, 98.6%, 87.9%, and 100%, respectively, and this therapy was tolerated. Multivariate analysis indicated that renal dysfunction was significantly associated with a non-SVR (odds ratio, 6.963; 95% confidence interval, 1.494-32.41; P = 0.013). The patients with renal dysfunction were older, had advanced liver fibrosis, lower baseline platelet and hemoglobin levels, and a higher rate of RBV dose reduction. Sofosbuvir and RBV therapy is highly effective and safe for genotype 2 HCV-infected Japanese patients. However, attention should be paid to baseline renal function when SOF- and RBV-containing regimens are used for patients with renal dysfunction.

Clinical features and CKD-related quality of life in patients with CKD G3a and CKD G3b in China: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE)

BackgroundThis study aimed to compare clinical features and health-related quality of life (HRQoL) in the Chinese chronic kidney disease (CKD) 3 population and determined the necessity of the subdivision of CKD3 in Chinese patients with CKD.MethodsParticipants with stage 3 CKD (18–74 years of age) were recruited at 39 clinical centers located at 28 cities in 22 provinces of China. The sociodemographic status, medical history, anthropometric measurements, and lifestyle behaviors were documented at entry, and blood and urine samples were collected. The estimated glomerular filtration rate was calculated using the CKD-EPI creatinine equation. The HRQoL was evaluated using the kidney disease quality-of-life instrument. A linear regression model was used to estimate the association between HRQoL and CKD stages (G3b vs G3a).ResultsThe levels of intact parathyroid hormone, systolic blood pressure, uric acid, and high-density lipoprotein cholesterol were statistically significantly higher, whereas the levels of serum bicarbonate and hemoglobin were statistically significantly lower in the G3b group compared with the G3a group. Compared with CKD G3a group, the proportions of subjects with hyperuricemia and anemia were significantly higher in CKD G3b group (61.4% vs. 52.0% and 26.4% vs. 17.9%, respectively, P< 0.01). The HRQoL scores in “physical functioning (PCS)”, “symptoms and problems”, “effects of the kidney disease” and “burden of the kidney disease” were statistically significantly lower in the CKD G3b group compared with the CKD G3a group (90.88 ± 11.05 vs. 89.30 ± 11.52, 88.29 ± 11.94 vs. 86.49 ± 13.45, 55.86 ± 26.40 vs. 52.10 ± 27.64, 46.56 ± 8.16 vs. 44.51 ± 9.22, respectively, P< 0.01). Further, CKD G3b was associated with a lower score of physical functioning compared with G3a (regression coefficient =−1.12 [95%CI: −2.23, −0.16]).ConclusionsThe preliminary results of this study suggested that modest differences existed in many important clinical features and KDQoL between patients with G3a and G3b CKD in a Chinese population. Also, a significant association between CKD3 subdivision of the disease and PCS was detected. Although further work is needed, we can speculate based on these results the CKD3 subdivision may be clinically meaningful for Chinese patients with CKD.

Measurements of renal shear wave velocities in chronic kidney disease patients.

Background Chronic kidney disease (CKD) patients have advanced glomerulosclerosis and renal interstitial fibrosis. Shear wave elastography (SWE) is useful to diagnose liver fibrosis. However, there are few data available regarding evaluation of kidney function on the use of SWE. Purpose To assess the utility of SWE by evaluating the correlation between renal function and renal elasticity using SWE. Material and Methods A total of 187 participants who had available serum creatinine levels and also underwent SWE of the kidney using a transabdominal ultrasonography were recruited at Nagoya University Hospital. We measured the depth of the shear wave (SW) in the right and left kidneys and calculated the measurement success rates. The glomerular filtration rate (GFR) classification and shear wave value (SWV) were compared. Results The success rates of the right and left kidneys were 93.6% and 71.6%, respectively. Based on these results, the correlation between GFR classification and SWV were analyzed in only the right kidneys because the success rates and the number of enrolled patients were low for the left kidney. There were significant differences found between G1 and G3a, G2 and G3a, G3a and G3b, G3a and G4, and G3a and G5. SWV significantly negatively and positively correlated with the G2-G3a and G3a-G3b classifications. Conclusion There is no correlation between renal function and SW. However, we can diagnose the progression to the CKD stages G3a and G3b by observing the changes over time using the SWV.

Dividing CKD stage 3 into G3a and G3b could better predict the prognosis of IgA nephropathy.

Chronic kidney disease (CKD) stage 3 was divided into stage G3a and stage G3b in the 2013 Kidney Disease Improving Global Outcomes guidelines. Whether it is appropriate to regard 45 mL/min/per 1.73 m2 as the threshold value of G3a/G3b staging and whether dividing CKD stage 3 into G3a/G3b plays a useful role in assessing the prognosis of patients with IgA nephropathy (IgAN) remain unknown. Three hundred and ninety patients from the First Affiliated Hospital of Zhengzhou University and Peking University First Hospital diagnosed with IgAN in CKD stage 3 were enrolled and successfully followed up. Cox proportional hazards model was used to analyze hazard ratios of reaching the composite endpoints (doubling of serum creatinine, end-stage renal disease: estimated glomerular filtration rate (eGFR) <15 ml/min/per 1.73 m2 or renal replacement therapy, or death) for patients with different eGFR and risk factors affecting composite endpoints. The Kaplan–Meier method was used to calculate the cumulative renal survival rate of patients. When eGFR was lower than 45 ml/min/per 1.73 m2, the hazard ratio increased sharply for patients in CKD stage 3 who reached the composite endpoints. Renal injury and prognosis were significantly different between patients in the G3a and G3b groups. Stage G3b was a major risk factor affecting prognosis. A threshold value of 45 ml/min/per 1.73 m2 appears appropriate to assess the prognosis of IgAN patients with CKD stage 3. Dividing IgAN patients with CKD stage 3 into G3a and G3b is very useful to help understand disease conditions and for predicting the risk for disease progression.

Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus-infected patients with renal impairment.

Hepatitis C virus (HCV) infection is a risk factor for end-stage renal disease, renal graft failure, and hemodialysis patient mortality. However, the efficacy of direct-acting antiviral therapy for HCV-infected patients with renal impairment is unclear. Additionally, the promising NS5B inhibitor sofosbuvir has not been recommended for patients with severe renal impairment. In this prospective, multicenter study, we evaluated the efficacy and safety of daclatasvir and asunaprevir combination therapy, with a focus on patients with renal impairment. The study included 322 genotype 1 HCV-infected patients who received daclatasvir and asunaprevir combination therapy. The safety and sustained virological response was examined at 12weeks after the end of treatment and safety was evaluated according to renal function. Of 322 patients, 5% (16/322) and 2.5% (8/322) had chronic kidney disease stage G3b (estimated glomerular filtration rate [eGFR], 30-44mL/min/1.73m2 ) and stage G4/5 (eGFR, 15-29/<15mL/min/1.73m2 ), respectively. Baseline presence of the NS5A resistance-associated variant, previous simeprevir treatment, and HCV RNA titers, which were predictors of a sustained viral response, were similar between patients with eGFR <45mL/min/1.73m2 and eGFR >45mL/min/1.73m2 . Notably, the 12-week sustained viral response rate was comparable in patients with eGFR <45mL/min/1.73m2 (100%, 24/24) and those with eGFR >45mL/min/1.73m2 (88.9%, 265/298; P = 0.07). Treatment discontinuation rates and adverse events, including alanine aminotransferase elevation, anemia, and renal disorders, were similar between the two groups. Daclatasvir and asunaprevir combination therapy for patients with renal dysfunction was highly effective and safe.