Chronic Kidney Disease Stage-3 Research Articles

Effects of sodium-glucose cotransporter-2 inhibitors on chronic kidney disease progression: a multi-state survival model

BackgroundCurrent guidelines recommend good glycemic control in patients with type 2 diabetes (T2D) to limit the progression of associated complications with combination therapies. This study aimed to compare the rate of chronic kidney disease (CKD) progression between patients who did or did not receive sodium-glucose cotransporter-2 inhibitors (SGLT2i) using a multistate model with two intermediate states (i.e., CKD stage 4 (CKD4) and 5 (CKD5)) and one absorbing state (i.e., death).MethodsData from patients with T2D and CKD stage 3 (CKD3) were retrieved for analysis. Patients treated with SGLT2i were matched 1:2 by prescription date with non-SGLT2i patients. The multistate model was constructed from Cox survival regression models specific to each transition stage. Cumulative failure and transition probabilities were estimated from bootstrapping.ResultsData from 6582 patients (2194 and 4388 patients in the SGLT2i and non-SGLT2i groups, respectively) were analyzed. At 10-year follow-up, patients in the SGLT2i group were more likely to remain at CKD3 compared to the non-SGLT2i group: 82.3% (95% CI 79.9%, 84.6%) vs 60.4% (57.6%, 63.4%). Transition probabilities to CKD4, CKD5, and death were lower in the SGLT2i group than non-SGLT2i group: 11.3% (9.5%, 13.3%) vs 19.8% (17.4%, 22.2%), 2.4% (1.5%, 3.4%) vs 7.4% (5.8%, 9.0%), and 4.1% (2.9%, 5.3%) vs 12.4% (10.3%, 14.6%), respectively.ConclusionSGLT2i may delay the decline in renal function and slow CKD progression compared to standard care without SGLT2i.

Evaluation of Neutrophil-Lymphocyte Ratio as Inflammatory Marker in Chronic Kidney Disease Stage 3 and 4

Chronic kidney disease (CKD) is a worldwide health problem because of the significant morbidity and mortality which is mostly due to chronic inflammation and proteinuria. Early detection of inflammation and its proper management can prevent further CKD progression and complications. This study aims to observe the association of neutrophil-lymphocyte ratio (NLR) with inflammatory markers in chronic kidney disease stage 3 and 4. In this study, a total of 100 adult patients of CKD stage-3 and 4 were included as study subjects and patient with acute illness, known case of malignancy, cardiovascular and cerebrovascular disease were excluded from the study. From each patient all the relevant history, clinical and laboratory findings were recorded in the data collection sheet. Study subjects were divided into two groups according to NLR value; those who have NLR 0- 3 were in group normal NLR and subjects with NLR >3 in group high NLR. Then markers of inflammation ESR, CRP and serum albumin were compared between these groups. Statistical analysis was done by Statistical Package for Social Science (SPSS) version 22.0. The mean ESR of male and female patients was higher in high NLR subjects than normal NLR subjects. The mean CRP was higher in high NLR subjects than normal NLR subjects. The mean serum albumin was lower in high NLR subjects than normal NLR subjects. The difference of mean ESR, CRP was statistically significant between high NLR and normal NLR subjects but difference of mean serum albumin was not statistically significant. The study findings suggest that high NLR is significantly associated with of inflammatory markers-ESR, CRP. Hence, it can be concluded that NLR could be used as an indicator of inflammation in CKD. Mugda Med Coll J. 2024; 7(1): 4-8

The ICD-9 to ICD-10 transition has not improved identification of rapidly progressing stage 3 and stage 4 chronic kidney disease patients: a diagnostic test study

BackgroundThe International Classification of Diseases (ICD) coding system is the industry standard tool for billing, disease classification, and epidemiology purposes. Prior research has demonstrated ICD codes to have poor accuracy, particularly in relation to rapidly progressing chronic kidney disease (CKD) patients. In 2016, the ICD system moved to revision 10. This study examines subjects in a large insurer database to determine the accuracy of ICD-10 CKD-staging codes to diagnose patients rapidly progressing towards end-stage kidney disease (ESKD).Patients and methodsSerial observations of outpatient serum creatinine measurements from 2016 to 2021 of 315,903 patients were transformed to estimated glomerular filtration rate (eGFR) to identify CKD stage-3 and advanced patients diagnosed clinically (eGFR-CKD). CKD-staging codes from the same time period of 59,386 patients and used to identify stage-3 and advanced patients diagnosed by ICD-code (ICD-CKD). eGFR-CKD and ICD-CKD diagnostic accuracy was compared between a total of 334,610 patients.Results5,618 patients qualified for the progression analysis; 72 were identified as eGFR rapid progressors; 718 had multiple codes to qualify as ICD rapid progressors. Sensitivity was 5.56%, with positive predictive value (PPV) 5.6%. 34,858 patients were diagnosed as eGFR-CKD stage-3 patients; 17,549 were also diagnosed as ICD-CKD stage-3 patients, for a sensitivity of 50.34%, with PPV of 58.71%. 4,069 patients reached eGFR-CKD stage-4 with 2,750 ICD-CKD stage-4 patients, giving a sensitivity of 67.58%, PPV of 42.43%. 959 patients reached eGFR-CKD stage-5 with 566 ICD-CKD stage-5 patients, giving a sensitivity of 59.02%, PPV of 35.85%.ConclusionThis research shows that recent ICD revisions have not improved identification of rapid progressors in diagnostic accuracy, although marked increases in sensitivity for stage-3 (50.34% vs. 24.68%), and PPV in stage-3 (58.71% vs. 40.08%), stage-4 (42.43% vs. 18.52%), and stage-5 (35.85% vs. 4.51%) were observed. However, sensitivity in stage-5 compares poorly (59.02% vs. 91.05%).

Effect of active vitamin-D on left ventricular mass index: Results of a randomized controlled trial in type 2 diabetes and chronic kidney disease

Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD). We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n=19, placebo n=26). Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints. The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.

Non-Renal Factors Associated with Simultaneous Liver-Kidney Transplant in Patients with End-Stage Liver Disease and Stage 3-5 Chronic Kidney Disease Not Requiring Dialysis

We aimed to identify the non-renal risk factors for simultaneous liver-kidney transplantation (SLKT) vs. liver transplantation alone (LTA) in end-stage liver disease (ESLD) patients with estimated glomerular filtration rate (eGFR) <60 ml/min, not on dialysis. Using organ procurement and transplantation network data, we studied adult ESLD patients who received deceased-donor SLKT or LTA in July 2002-Mar 2016 with a 4-point modification of renal disease (MDRD) equation-estimated glomerular filtration rate (eGFR) stratified into chronic kidney disease stage 3 (CKD-3): 30-59 ml/min, CKD stage 4 (CKD-4): 15-29 ml/min, and CKD stage 5 (CKD-5): <15 ml/min) and not on maintenance dialysis (NOD). The outcome of the study was identification of non-renal risk factors predicting likelihood of SLKT vs. LTA. We reported the odds ratio (OR) and 95% confidence interval (CI) for SLKT vs. LTA associated with important clinical variables. Strong non-renal (non-creatinine-associated) risk factors for SLKT were WL-time >2 yrs. and 1-2 yrs. (OR = 3.80, CI = 2.94-4.91; OR = 3.20, CI = 2.58-3.97; respectively), African American or Hispanic recipient race/ethnicity (OR = 2.93, CI = 2.45-3.51; OR = 1.46, CI = 1.24-1.72; respectively), liver repeat transplant (OR = 1.66, CI = 1.39-1.99), and diabetes (OR = 1.53, CI = 1.36-1.72). Factors associated with lower likelihood of SLKT were donor age >60 years (OR = 0.25, CI = 0.19-0.32), female recipient sex (OR = 0.48, CI = 0.43-0.54), hepatocellular carcinoma (OR = 0.53, CI = 0.35-0.81), and transplant center procedure volume tercile ranks 3<sup>rd</sup> (OR = 0.74, CI = 0.62-0.89) and 2<sup>nd</sup> (OR = 0.78, CI = 0.64-0.95). Model for end-stage liver disease scores have varying associations with SLKT vs. LTA, depending on calculation time: at wait listing or transplant. CKD-5 and -4 at wait listing (WL) and transplant were the risk factors with highest point estimates for SLKT vs. LTA. In patients with ESLD and CKD stage 3-5, not on dialysis, strong non-renal risk factors favoring SLKT versus LTA include: prolonged waitlist time, African American or Hispanic race/ethnicity, previous liver transplant, and diabetes. Some novel associations found between risk factors and likelihood of SLKT need further study for confirmation. Lack of uniform criteria for SLK allocation during the period studied is a major limitation of the study.

Economic burden of secondary hyperparathyroidism in Germany: a matched comparison

PurposeSecondary hyperparathyroidism (SHPT) of renal origin is a progressive complication in chronic kidney disease (CKD) and is associated with serious osseous and non-osseous complications, CKD progression, and economic burden for healthcare systems worldwide. We aimed at assessing characteristics, healthcare resource utilization, and costs of incident SHPT patients in CKD stage 3 (CKD3) and 4 (CKD4), using administrative claims data.MethodsGerman claims data were used to identify CKD3 and CKD4 patients, who were stratified by the occurrence of incident SHPT. Patients with SHPT were matched 1:1 to non-SHPT patients with the same CKD stage using propensity scores. Matched groups were compared during a 2-year follow-up period.ResultsOverall, 1156 CKD3 and 517 CKD4 incident SHPT patients and their respective matches were identified. Mean number of all-cause hospitalizations were significantly higher among SHPT patients (2.7 vs. 2.0 in CKD3, 2.8 vs. 1.5 in CKD4) during follow-up. Similarly, the mean number of outpatient encounters was significantly higher among the SHPT cohorts (95.0 vs. 64.3 in CKD3, 101.4 vs. 49.8 in CKD4). SHPT patients progressed to CKD5 more often (6.1% vs. 1.2% from CKD3, 26.7% vs. 2.9% from CKD4, both P < 0.01) resulting in a higher proportion of dialysis (6.1% vs. 1.3% in CKD3, 22.1% vs. 3.7% in CKD4, both P < 0.01). Consequently, average all-cause healthcare costs significantly increased per patient (€19,477 vs. €15,115 in CKD3, €25,921 vs. €12,265 in CKD4).ConclusionsPatients with CKD3&4 and incident SHPT of renal origin presented with significantly higher healthcare resource utilization and costs, as well as increased disease progression compared to non-SHPT patients.

MO515CONSTIPATION IN CHRONIC KIDNEY DISEASE: PREVALENCE AND RISK FACTORS

Abstract Background and Aims Among various gastrointestinal disorders, constipation is one of the most common symptom in chronic kidney disease (CKD). However it is often neglected by nephrologists as self-limiting condition. Constipation impacts quality of life in multiple ways and increases socio-psychological burden. Constipation and associated risk factors have been poorly studied and most studies are retrospective. Method We enrolled CKD stage 3 to 5 patients on regular follow-up with nephrologist from June 2018 to June 2020, at a tertiary care centre in North India. Constipation was defined using Rome IV criteria (Functional constipation) which is composed of six constipation related symptoms, and diagnosis of constipation is established by presence of two or more symptoms for at least 3 months. Patients were also asked to maintain a 7 day prospective stool diary. It consisted of seven day written prospective chart of stool form and frequency. Patients were instructed to record when each bowel movement happened and to mark stool form type for each movement as described in words and pictures on Bristol Stool Form Scale (BSFS). Opioid induced constipation was defined as per Rome IV criteria. The diagnostic criteria is similar to functional constipation, but with requisite that new or worsening symptoms occurred when initiating, changing or increasing opioid therapy. Results Two hundred twenty five patients were studied out of which 59 (26.2%) patients were in CKD stage3, eighty one (36%) patients were in CKD stage4 and 85 (37.8%) patients were in stage5. Out of 85 CKD stage5 patients, 23 (27%) were on dialysis. Mean age of patients was 49.1 years. Out of 225 patients, 135 (60%) were male. Constipation symptoms and diagnosis reported in each stage has been depicted in Table 1. Clinical correlates of constipation has been depicted in Table 2. Conclusion Constipation measured using Rome IV criteria affects around two-third of CKD stage 3-5 patients. Diabetes, hypertension and opioid use has been found to be significantly associated with constipation.

1049-P: Preexisting Chronic Kidney Disease Stage 3 Does Not Reduce Glycemic Efficacy of Metformin in U.S. Veterans with Type 2 Diabetes

Background: Metformin (MET) is approved for treatment of type 2 diabetes (T2D) in patients with chronic kidney disease stage 3 (CKD3); however, data on its glycemic efficacy in CKD3 is lacking. Methods: This was a retrospective study including 85,997 U.S. veterans with T2D and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2 treated with MET monotherapy with adequate adherence (defined by proportion of days covered ≥80%) between 01/2010 and 08/2018. CKD3 was defined as eGFR 30-59 ml/min/1.73m2. Twelve-month time-averaged A1c changes from baseline were compared in patients without and with CKD3 using univariate and multivariate linear regression analyses adjusted for case-mix. Results: The mean±SD age for the total cohort was 60.8±9.9 yrs, 95.2% were males, 76.3 and 13.0% were Whites and Blacks, respectively. Average daily mean±SD MET dose was 1341±202 mg. Pre-existing CKD3 was present in 7,566 (9.7%) of individuals. Baseline characteristics by CKD3 status are shown in Table 1. In unadjusted analysis, mean A1c reduction was 0.59±1.0 vs. 0.52±0.9 % in patients without and with CKD3 (p&amp;lt;0.001). The difference in A1C between two groups was lost after adjustments for baseline characteristics and MET dose (p=0.058). Conclusions: In this large retrospective study, presence of preexisting CKD stage 3 did not affect glycemic efficacy of metformin monotherapy in T2D patients. Disclosure E. Gosmanova: None. D.E. Gemoets: None. L.S. Kaminsky: None. C.P. Kovesdy: Consultant; Self; Amgen, AstraZeneca, Bayer AG, Cara Therapeutics, Reata, Takeda Pharmaceutical Company Limited, Tricida. A.R. Gosmanov: None.

Progressive Decline in Estimated Glomerular Filtration Rate in Patients With Diabetes After Moderate Loss in Kidney Function-Even Without Albuminuria.

Persons with diabetes but no chronic kidney disease (CKD) and without albuminuria have the same age-related decline in kidney function as the background population. Whether this also applies following moderate loss in kidney function is unknown. We quantified the impact of albuminuria status on the development of estimated glomerular filtration rate (eGFR) trajectories following CKD stage 3 (CKD3) and assessed potential heterogeneous development patterns among the subgroup with normoalbuminuria. We used repeated clinical measures during up to 16 years of follow-up in 935 persons with type 1 diabetes and 1,984 with type 2 diabetes. Trajectories of eGFR by diabetes type and albuminuria status following CKD3 were estimated with spline mixed-effects models with adjustment for relevant confounders. Latent class trajectory modeling was used to find distinct patterns of eGFR development in the subgroups with normoalbuminuria. Mean annual declines in eGFR for normo-, micro- and macroalbuminuria the first 10 years following CKD3 were 1.9, 2.3, and 3.3 mL/min/1.73 m2 in type 1 diabetes and 1.9, 2.1, and 3.0 in type 2 diabetes, respectively. For normoalbuminuria, two distinct eGFR patterns were found, one with accelerated declining eGFR levels. This specific progression pattern was associated with less use of lipid-lowering treatment, renin-angiotensin system blockers, and other antihypertensive treatment. Our results support a diabetes-dependent decline in kidney function without albuminuria following CKD3, with a subgroup showing a progressive decline. Furthermore, this group seems to be undertreated in terms of cardioprotective and renal protective treatment and suggests that increased attention should be drawn to normoalbuminuric diabetic kidney disease.

The use of Free Style Libre Continues Glucose Monitoring (FSL-CGM) to monitor the impact of Ramadan fasting on glycemic changes and kidney function in high-risk patients with diabetes and chronic kidney disease stage 3 under optimal diabetes care

AimTo understand the risk of hypoglycaemia during Ramadan fasting by use of CGM, as well as to observe the Glycemic control and renal functions in patients with diabetes and chronic kidney disease stage 3 (CKD-3). MethodA prospective interventional study conducted in the Dubai Hospital, a tertiary care centre in the United Arab Emirates, during the month of Ramadan 1437 AH (Hijri), which corresponded to June 6th till July 5th, 2016. 25 patients with type 2 diabetes and stage 3 chronic kidney disease (CKD stage 3) were included in the study, who intended to fast during Ramadan. The aim was to observe the serum glucose level through 24 h FreeStyle Libre flash continuous glucose monitor (FSL-CGM). Most patients had three sensors during the study, covering an average three weeks during Ramadan and three weeks outside Ramadan (Sha'ban and shawal). We also monitored the change in, BP, HBA1c, kidney functions and BMI before and after Ramadan. ResultsThis study included 25 adults with a mean age of 60 (±14 years). Fasting Ramadan did not result in any significant change in biophysical and biochemical profile of these patients. Data from FSL-CGM showed significantly longer duration (101.9 ± 119.1 Vs. 45.9 ± 47.6 min, p < 0.033) and more frequent hypoglycemic episodes (4.4 ± 4.7 Vs. 2.3 ± 3.0, p < 0.047) during Ramadan compared tonon-Ramadan respectively. The mean blood glucose readings were also significantly lower (70.7 ± 29.3 Vs.93.7 ± 57.9 mg/dl p < 0.011) during Ramadan compared to non -fasting period. The renal function mean ± SD (serum creatinine 1.48 ± 0.37, 1.44 ± 0.37 and eGFR, 49.0 ± 18.4, 48.9 ± 17.5 p 0.9) showed no significant change due to fasting. ConclusionIn patients with diabetes and CKD-stage 3 Ramadan fasting under close supervision and optimal diabetes care, was not associated with worsening of HBA1c and renal function. Patients had significantly more frequent and prolonged hypoglycemic episodes during Ramadan.

Serum sclerostin as a potential novel biomarker for heart valve calcification in patients with chronic kidney disease.

To explore the correlation between change in sclerostin level and heart valve calcification in patients with chronic kidney disease (CKD) in stages 3-5, as well as the possible underlying mechanism, which could provide a clinical reference for the diagnosis and treatment of cardiovascular disease (CVD). 110 patients were divided into a healthy control group and three groups of patients with CKD stages 3, 4, and 5 according to CKD staging guidelines. Scr, BUN, AKP, TC, TG, HDL, LDL, Ca, Pi, and CRP were measured, and calcium-phosphate product (Ca×Pi) calculated. ELISA was used to measure the sclerostin level, and the estimated glomerular filtration rate (eGFR) was calculated by MDRD. Heart valve calcification was measured by a physician in the Cardiac Department of our hospital. The correlations between sclerostin-level change and heart valve calcification, as well as each index in CKD patients in stages 3-5, were analyzed. Compared with the healthy control group, the serum Ca in CKD stage-3, stage-4, and stage-5 groups (p < 0.05) was reduced, and PTH was increased (p < 0.05). Blood Pi and Ca×Pi in the stage-4 and stage-5 groups were increased (p < 0.05). The serum sclerostin level increased with renal hypofunction in stage-3 CKD patients, and was significantly increased compared with that of the control group, reaching the highest level in the terminal stage (p < 0.01). Pearson correlation analysis indicated that serum sclerostin was negatively correlated with eGFR (r = -0.91, p < 0.001) and blood Ca (r= -0.271, p < 0.001), and positively correlated with SCr (r = 0.608, p < 0.001), blood Pi level (r = 0.295, p < 0.001), PTH (r = 0.334, p < 0.001), and Ca×Pi (r = 0.275, p < 0.001). The rate of heart valve calcification in the CKD patients in stage 5 was relatively high (11/30, 36.67%), and significantly higher than that in healthy controls (1/20, 5%; p < 0.01). Logistic regression analysis of heart valve calcification indicated that sclerostin was a risk factor for heart valve calcification in CKD patients in stages 3-5. The sclerostin level gradually increased with renal hypofunction in CKD patients in stages 3-5, and the increase in serum sclerostin level in the CKD patients occurred earlier than the change in Pi and Ca×Pi. The risk of heart valve calcification in stage-5 CKD patients was significantly increased. Sclerostin is an independent risk factor for heart valve calcification in CKD patients.

Diffusion-weighted imaging for staging chronic kidney disease: a meta-analysis.

Objective:To evaluate stages of chronic kidney disease (CKD) by apparent diffusion coefficient (ADC) obtained from diffusion weighted imaging (DWI) using a meta-analysis.Methods:Literature databases were searched from PubMed, Web of Science, Cochrane and Embase to identify relevant articles about DWI in CKD between 1999 and 2017. ADC values were extracted from the healthy group and CKD patients with different stages. Meta-analysis was conducted using STATA v. 12.0. A random-effects model was performed to acquire the effect estimate, which was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI). We performed comparisons of ADC values between the following groups: (1) the ADC values of the normal kidneys v s earlier Stage 1–2 of CKD; (2) Stage 3 v s the Stage 1–2 of CKD; (3) the Stage 4–5 v s the Stage 3.Results:Six studies were included in this meta-analysis. The CKD patients with earlier Stage 1–2 showed lower ADC values than the healthy subjects [WMD = −0.09, 95% CI(−0.12 to −0.06), p < 0.001]. However, no obvious difference in ADC values was found between the Stage 3 and Stage1–2 of CKD [WMD = −0.09, 95% CI (−0.18 to 0.01), p = 0.08]. The CKD Stage3 had higher ADC values than those of Stage4–5 [WMD = −0.21, 95% CI (−0.32 to −0.11), p = 0.01].Conclusion:DWI is an accurate and non-invasive imaging technique for early diagnosis and staging of CKD. Quantitative DWI may potentially play a role in making clinical decisions in the follow-up of CKD.Advances in knowledgeDWI can be a valuable tool for staging of CKD.

HCV treatment initiation in persons with chronic kidney disease in the directly acting antiviral agents era: Results from ERCHIVES.

Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. We identified HCV+ persons in ERCHIVES between October 1999 and July 2016. We excluded HIV+ and HBsAg+ and those with missing baseline HCV RNA and baseline eGFR data. We identified persons initiated on any approved DAA-regimen through July 2016, by CKD stage. Logistic regression analyses were used to determine factors associated with treatment initiation. Among 83706 evaluable persons, 21.1% initiated treatment. Rates differed significantly by CKD stage: 22.1% for eGFR>90mL/min/1.73m2 and CKD stage-2; 14.9% for CKD stage 3; and 8.0% for CKD stage-4/5. Those with CKD stage-3 were 33% less likely and those with CKD stage-4/5 were 60% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90mL/min/1.73m2 . Treatment initiation was less likely in HCV genotype 2 (OR 0.59; 95%CI 0.53,0.66) or 3 (OR 0.53; 95%CI 0.47,0.61) and those with diabetes (OR 0.87, 95% CI 0.81,0.94), cardiovascular disease (OR 0.77, 95% CI 0.70,0.84), alcohol abuse or dependence (OR 0.74, 95% CI 0.70,0.79) or cirrhosis (OR 0.86, 95% CI 0.80,0.92) at baseline. Persons with more advanced CKD are less likely to receive treatment for HCV despite recent data on safety and efficacy. Strategies are needed to improve treatment rates in the HCV/CKD population.

Study of oxidant and anti-oxidant status in patients with chronic kidney disease

Background: Chronic kidney disease (CKD) is associated with oxidative stress (OS), which occurs even in early stages of CKD and was shown to further contribute to progression of renal dysfunction and increased cardiovascular risk in CKD patients. Majority of studies have evaluated OS in CKD patients using limited biomarkers. Present study aimed at comprehensive evaluation of oxidant and antioxidant status in CKD patients. Methods: 120 patients diagnosed with CKD who were classified into three groups of 40 each [group-1 (CKD stage1 and 2), group-2 (CKD stage3 and 4) and group-3 (CKD stage 5] based on eGFR and 30 healthy controls were recruited. Malondialdehyde (MDA), protein carbonyls (PC), ferric reducing ability of plasma (FRAP), protein thiols, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase were measured in all subjects. FRAP was corrected for uric acid (FRAP_UA) and MDA/FRAP_UA ratio was calculated. Score for oxidative stress (SOS) was calculated using the oxidant antioxidant parameters studied. Results: MDA, PC, MDA/FRAP_UA, FRAP and SOS were higher whereas protein thiols, SOD, GPx and catalase were lower in CKD patients than controls. Further, MDA, PC and FRAP and SOS increased progressively and protein thiols, SOD and catalase decreased progressively with increasing renal dysfunction. MDA, PC, FRAP and SOS showed positive correlation with creatinine and negative correlation with eGFR, whereas protein thiols, SOD, and catalase showed positive association with eGFR and negative correlation with creatinine. Conclusions: CKD patients are prone for oxidant injury which increases progressively with worsening renal dysfunction and is associated with degree of renal impairment. Score for oxidative stress helps in comprehensive assessment of oxidative stress in CKD patients.

HCV Treatment Initiation in Patients with Chronic Kidney Disease: Results from ERCHIVES

Background Newer directing antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether availability of these newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown.Methods We identified HCV+ persons in ERCHIVES. We excluded HIV+ and HBsAg+ and those with missing HCV RNA and eGFR data. We determined the CKD stage according to National Kidney Foundation criteria. We determined the number of persons initiated on any of the approved DAA-regimen (defined as >14 days of DAA prescription). Logistic regression analyses was used to determine factors associated with treatment initiation.ResultsAmong 76,513 evaluable persons, 21.1% initiated DAA treatment. Initiation rates differed significantly by CKD stage: 21.1% (15,136/68,469) for eGFR>90mL/minute/1.73m2 and CKD stage-2; 14.0% 9853/6,086) for CKD stage 3; and 7.6% (148/1,958) for CKD stage-4/5. Those with CKD stage-3 were 35% less likely and those with CKD stage-4/5 were 65% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90mL/minute/1.73m2. Those with Body Mass Index (BMI)>30 were more likely to initiate treatment (OR 1.24, 95% CI 1.19,1.29). Treatment initiation was less likely in HCV genotype 2 or 3 and those with diabetes (OR 0.82, 95% CI 0.78,0.86), cardiovascular disease (OR 0.73, 95% CI 0.68,0.78), alcohol abuse or dependence (OR 0.75, 95% CI 0.72,0.78) or cirrhosis (OR 0.85, 95% CI 0.80,0.89) at baseline.Conclusion Persons with more advanced CKD are less likely to receive treatment for HCV. Strategies are needed to improve treatment rates in the HCV/CKD population.Disclosures A. Butt, Merck: Investigator, Grant recipient. A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary

Pretransplant Type 2 Hepatorenal Syndrome Is Associated With Persistently Impaired Renal Function After Liver Transplantation.

Type 2 hepatorenal syndrome (HRS2) is a functional renal impairment complicating end-stage liver disease. Although it is reversible after liver transplantation, long-term posttransplant outcomes in HRS2 patients remain ill-defined. Retrospective, matched case-control (1:2) study of all adult HRS2 patients transplanted in our institution between 2000 and 2012. The HRS2 patients were identified from our electronic transplant database, and matched with controls for the following variables: age, sex, etiology, diabetes mellitus, and year of transplant. Forty-two HRS2 patients were compared to 83 controls. At the time of transplant, HRS2 patients had an estimated glomerular filtration rate of 41 ± 1 mL/min per 1.73 m. The HRS2 patients had greater intraoperative packed red blood cell transfusion (P = 0.002), and longer intensive care unit (P = 0.01) as well as total hospital length of stay (P = 0.03). Reversal of HRS2 occurred in 88.1% patients, 5.7 ± 0.5 days after transplantation. Although HRS2 patients had lower initial exposure to calcineurin inhibitors, a greater proportion of HRS2 patients had chronic kidney disease stage 3 (CKD3) at 3 (53.8% vs 28.4%; P = 0.007) and 12 months (59.5% vs 38.2%; P = 0.03) compared to controls. One-year survival was similar between the 2 groups (log-rank P = 0.82). On multivariate analysis, pretransplant HRS2 was associated with CKD3 at 3 (odds ratio, 3.73; 95% confidence interval, 1.54-9.03; P = 0.004) and 12 months (odds ratio, 3.23; 95% confidence interval, 1.37-7.64; P = 0.007) after transplantation. Liver transplantation reverses HRS2 in the majority of patients with survival outcomes comparable to matched controls, despite longer stays in intensive care unit and in hospital. Pretransplant HRS2 is associated with early posttransplant CKD3, despite calcineurin-inhibitor minimization.

Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease

Increased inflammation is common in patients with chronic kidney disease (CKD) and is associated with increased adverse cardiovascular events (CVE). Neutrophil-to-lymphocyte ratio (NLR) was used to predict survival in patients with acute coronary syndrome. We aimed to evaluate predictive ability of NLR in CKD patients. 225 subjects with stage 3-5 CKD were followed for a mean of 39 months. Fatal and nonfatal CVE were recorded during this period. NLR at baseline was determined from complete blood count differential. Endothelial dysfunction (flow-mediated dilation, FMD), hsCRP and insulin resistance were determined. We investigated if NLR could predict development of fatal and nonfatal CVE. We also looked at how NLR and its individual components change across CKD stages and whether NLR is related to CRP, insulin resistance and endothelial dysfunction. There were 70, 74 and 81 patients in groups of CKD stage-3, stage-4 and stage-5, respectively. Median NLR was 2.81. NLR showed a significant increase from stage 3 to stage 5. NLR was inversely associated with FMD independent of hsCRP. 14 fatal and 52 nonfatal CVE occurred during follow-up period. NLR could predict composite CVE independent of insulin resistance and hsCRP. Increased NLR over 2.81 was related to a significantly decreased survival time (log-rank Chi-square = 14.833, P < 0.0001). A cutoff value for NLR ≥3.76 could predict development of composite CVE with 80.3 % sensitivity and 91.8 % specificity. NLR is independently related to endothelial dysfunction and could predict composite cardiovascular endpoints independent of traditional confounding factors in patients with moderate to severe CKD.

Abstract 3460: Liver-type Fatty Acid-binding Protein Is A Promising Predictive Marker Of Contrast-induced Nephropathy

Contrast-induced nephropathy (CIN), a well-known complication of contrast media exposure for the patients with chronic kidney disease (CKD), may results from acute tubular necrosis. Although 4 to 11 percent with mild to moderate renal insufficiency develop CIN, there were no biological markers to more accurately predict the occurrence of CIN than the existing makers such as serum creatinine (sCr). Liver-type fatty acid-binding protein (L-FABP) as a novel maker, is an intracellular carrier protein of free fatty acids that marked upregulated and expressed abundantly in proximal tubules after renal ischemia.We prospectively investigated whether urinary L-FABP is an alternative maker of predicting CIN. Methods: We enrolled sixty-five patients (46 male, 71.8 ± 8.2years) undergoing scheduled coronary angiography who had mild kidney disease with CKD stage3 (glomelurar filtration ratio (GFR) &lt;60 ml/1.73 m 2 or albuminuria (u-Alb)≥ 300 mg/gCRE), treated with one-half isotonic (0.45 percent) saline between 12 hours before and after the procedure. We measured urinary L-FABP, u-Alb,β 2 -microglobulin, α 1 -microglobulin, sCr and NAG( N -acetyl-β-d-glucosaminidase). CIN was defined as an increase of sCr of &gt;25% or 0.5 mg/dl (44.2micromol/l) within 2 days of contrast. The cohort was divided into two groups according to occurrence of CIN; CIN-G and nonCIN-G. Results: CIN occurred in 4 of 65 patients (6%). Demographics, the pre-procedural level of makers (β 2 -microglobulin, α 1 -microglobulin, sCr, NAG) and used contrast volume are no significant differences between the two groups. Pre-procedural urinary L-FABP levels were significantly greater in CIN-G than in nonCIN-G(112.5 ± 81.4μg/g Cr;19.7 ± 43μg/g Cr; P&lt; 0.01) as well as u-Alb (CIN-G;1711.3 31386.6 mg/gCRE nonCIN-G; 192.3 3482.3 mg/gCRE Cr; P &lt; 0.01). On the basis of ROC curve of urinary parameters , u-Alb and urinary L-FABP had the significantly high predictive value than other markers(p&lt;0.05). Conclusion: Urinary L-FABP combined with u-Alb can be more accurate markers to predict the risk of CIN than other existing urinary parameters.