A Case Control Study of Risk Assessment of Diabetes and Nephropathy with eNOS (T786C and 27bp VNTR) Gene Polymorphisms.

OBJECTIVES: To determine the association of eNOS (T786C and 27bp VNTR) gene polymorphism with the risk of type II diabetes mellitus and diabetic nephropathy in North India. METHODS: The prospective case control study was conducted over a period of 18 months. A total of 100 patients of Type 2 Diabetes Mellitus (A1: 50 cases without Diabetic nephropathy-DN and 50 cases with DN) aged 18-75 years and 50 healthy adults as control (Group B) were included. The endothelial nitric oxide gene variant (T786C and 27bp VNTR) genotypes and alleles were studied. Odds ratio with 95% CI was calculated for genotype and alleles for the occurrence of diabetes and DN. p value of less than 0.05 was considered as significant. RESULTS: With Bb as reference(27bp VNTR), the odds ratio for Ab in the three groups (A1,A2,B) was 2.243, 1.545 and 0.746 respectively; and for Aa was 3.043, 3.058 and 1.878 respectively; with TT as reference (T786C), it was 1.573, 1.55 and 1.055 respectively for TC; and for CC it was 2.121, 2.063 and 2.348 respectively. The OR was comparable among the study groups and control for all genotypes and alleles (p>0.05). CONCLUSION: In conclusion, there was a trend towards higher predilection of DN with aa genotype and a allele in 27 VNTR, CC genotype and C allele of -786T>C polymorphism however it was not found to be statistically significant. Future large sample studies are required to account for the ethnic variation for a clearer association of the genes and their associated risk with Diabetes and its complications.

Health economic modelling of diabetic kidney disease in patients with type 2 diabetes treated with Canagliflozin in Belgium.

OBJECTIVES: The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial showed reduced renal and cardiovascular (CV) events in patients with type 2 diabetes (T2D) and diabetic kidney disease (DKD) treated with canagliflozin 100 mg added to Standard of Care (SoC) versus SoC alone. This led to an extension of the canagliflozin 100 mg European marketing authorisation, making canagliflozin the first pharmacological therapy to receive authorisation for the treatment of DKD since the RENAAL and IDNT trials more than 20 years ago. Given the importance of cost-effectiveness analyses in health care, this study aimed to leverage the CREDENCE trial outcomes to estimate the cost-effectiveness of canagliflozin 100 mg from the perspective of the Belgian healthcare system. METHODS: A microsimulation model (CREDENCE Economic Model of DKD), developed using patient-level CREDENCE trial data, was leveraged to model the progression of DKD and CV outcomes, associated costs, and life quality. Unit costs and quality-adjusted life years (QALYs) were sourced from the literature. The time horizon was 10 years and sensitivity analyses were performed. RESULTS: Canagliflozin was associated with sizable gains in life-years and QALYs over 10 years, and the incremental cost-effectiveness ratio cost offsets associated with reductions in CV and renal complications resulted in overall net cost savings from the perspective of the Belgian healthcare system. CONCLUSION: Model-based results suggest that adding canagliflozin 100 mg to SoC can improve outcomes for patients with DKD while reducing overall net costs for the Belgian healthcare system.

Direct medical cost of nephropathy in patients with type 2 diabetes.

INTRODUCTION: Although it is known in the literature that the medical cost due to the complications of diabetes mellitus (DM) is high, data about the effect of diabetic kidney disease (DKD) on medical cost are limited. AIMS: The aim of this study is to investigate the cost of hospitalized patients with nephropathy due to type 2 DM, the parameters closely related to this cost and the effect of diabetic nephropathy stage on medical hospitalization costs. METHODS: The study group consisted of 141 patients with DKD, and the control group consisted of 111 patients with DM without chronic complications in this retrospective study. The demographic characteristics, duration of diabetes and HbA1c values of the patients were recorded at the time of their first hospitalization, medical hospitalization costs, and the length of stay in hospital were recorded for a year from the date of hospitalization. The total medical hospitalization costs of the patients were divided into two groups as cost of medications and supplies and service cost. Patients with DKD were compared according to their dialysis status and nephropathy stages. RESULTS: While the average cost of a patient with DKD was 603 (283-1267) United States Dollars (USD), the average cost of a DM patient without complications was 222 (141-292) USD (p < 0.05). It was observed that the patients with DKD had higher medical hospitalization costs and length of stay in hospital compared to patients with diabetes without complications. In addition, it was observed that the medical hospitalization costs and the length of stay in hospital were significantly higher in patients undergoing dialysis than patients who did not undergo dialysis (p < 0.05 for each). An independent relation was found between average cost and duration of diabetes in patients with DKD (p < 0.05). No relation was found between diabetic nephropathy stage and medical hospitalization costs (p > 0.05 for each). CONCLUSION: The estimated cost of treatment of DKD is higher than patients with uncomplicated diabetes. If preventive measures are not taken for DKD, it will continue to be a heavy economic burden.

Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease: an exploratory study.

BACKGROUND: A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina's Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10-8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. RESULTS: Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-ß signalling and Th17 cell differentiation. CONCLUSIONS: Epigenetic alterations provide a dynamic link between an individual's genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.

Albuminuria Testing by Race and Ethnicity among Patients with Hypertension with and without Diabetes.

BACKGROUND: Detection of chronic kidney disease (CKD) with urine albumin-to-creatinine ratio (UACR) among patients with hypertension (HTN) provides an opportunity for early treatment, potentially mitigating risk of CKD progression and cardiovascular complications. Differences in UACR testing patterns among racial/ethnic populations at risk for CKD could contribute to known disparities in CKD complications. METHODS: We examined the prevalence of UACR testing among low-income adult primary care patients with HTN, defined by a new administrative code for HTN or 2 clinic blood pressures >140/90 mm Hg between January 1, 2014, and January 1, 2017, in one public health-care delivery system with a high prevalence of end-stage kidney disease among race/ethnic minorities. Logistic regression was used to identify odds of UACR testing within 1 year of a HTN diagnosis, overall, and by racial/ethnic subgroup, adjusted for demographic factors, estimated glomerular filtration rate, and HTN severity. Models were also stratified by diabetes status. RESULTS: The cohort (n = 16,414) was racially/ethnically diverse (16% White, 21% Black, 34% Asian, 19% Hispanic, and 10% other) and 51% female. Only 35% of patients had UACR testing within 1 year of a HTN diagnosis. Among individuals without diabetes, odds of UACR testing were higher among Asians, Blacks, and Other subgroups compared to Whites (adjusted OR [aOR] 1.19; 95% CI 1.00-1.42 for Blacks; aOR 1.33; 1.13-1.56 for Asians; aOR 1.30; 1.04-1.60 for Other) but were not significantly different between Hispanics and Whites (aOR 1.17; 0.97-1.39). Among individuals with diabetes, only Asians had higher odds of UACR testing compared to Whites (aOR 1.35; 1.12-1.63). CONCLUSIONS: Prevalence of UACR testing among low-income patients with HTN is low in one public health-care delivery system, with higher odds of UACR testing among racial/ethnic minority subgroups compared to Whites without diabetes and similar odds among those with diabetes. If generalizable, less albuminuria testing may not explain higher prevalence of kidney failure in racial/ethnic minorities.

Cause of kidney disease and cardiovascular events in a national cohort of US patients with end-stage renal disease on dialysis: a retrospective analysis.

AIMS: End-stage renal disease (ESRD) is a strong cardiovascular risk factor. We aimed to determine the extent to which cause of kidney disease independently contributes to this risk. METHODS AND RESULTS: Using a national US ESRD registry, we selected patients with eight different causes of ESRD who initiated dialysis 1997-2014. We used proportional sub-distribution hazard models, with non-cardiovascular death or kidney transplantation as competing risks, to estimate hazard ratios (HRs) for a first composite cardiovascular event (myocardial infarction, ischaemic stroke, or cardiovascular or cerebrovascular death), by cause of ESRD. The population was restricted to those using Medicare insurance at Day 91 after dialysis initiation (when most patients become Medicare eligible). Outcomes were ascertained from Medicare claims or Death Notifications. Among the 658 168 patients identified, composite event rates ranged from 3.5/100 person-years in IgA nephropathy to 14.6/100 person-years in diabetic nephropathy (DN). After adjusting for demographics, socioeconomic factors, comorbidities, dialysis modality, and laboratory values, cardiovascular event HRs differed significantly by cause of ESRD. Comparing to IgA nephropathy, the adjusted HR was highest for DN [aHR = 2.97, 95% confidence interval (CI) 2.77-3.20], next highest for lupus nephritis (aHR = 1.86, 95% CI 1.71-2.03), and thereafter ranged from 1.29 (95% CI 1.19-1.39) in autosomal dominant polycystic kidney disease to 1.67 (95% CI 1.52-1.83) in membranous nephropathy. CONCLUSION: High cardiovascular event rates in dialysis patients vary considerably by cause of ESRD. Determining underlying reasons for these differences might provide new insights in to cardiovascular disease mechanisms as well as inform future drug development and clinical trial design.

Assessment of the Relationship between Carotid Intima-Media Thickening and Early-Stage Diabetic Kidney Disease Coupled with Helicobacter pylori Infection.

OBJECTIVE: This study aimed to explore the associations between carotid intima-media thickness (CIMT) and early-stage diabetic kidney disease (DKD) coupled with Helicobacter pylori (H. pylori) infection in type 2 diabetic patients. METHODS: A cross-sectional study including 180 type 2 diabetic participants was conducted to explore the associations between CIMT and early-stage DKD coupled with H. pylori infection, and a stepwise multivariate regression analysis evaluated the correlations of CIMT with clinical and serologic parameters. RESULTS: The type 2 diabetic patients with early-stage DKD coupled with H. pylori infections had the highest CIMT values. Apolipoprotein B (ApoB), urine albumin/creatinine ratio (UACR), and interleukin-6 (IL-6) were independent predictors of CIMT. CONCLUSIONS: Early-stage DKD coupled with H. pylori infection may synergistically lead to significant CIMT thickening in type 2 diabetic patients. Additionally, ApoB, UACR, and IL-6 levels were important independent risk factors for increased CIMT.

Preclinical assessment of utility of M6S for multimodal acute and chronic pain treatment in diabetic neuropathy.

AIMS: Previous reports from our laboratory have established that morphine-6-O-sulfate (M6S) is a mixed µ/δ opioid receptor (OR) agonist and a potential improved alternative to morphine for treatment of chronic multimodal pain in non-diabetic rats. This study extends the antinociceptive effects of M6S and morphine in STZ-induced diabetic rats. MATERIALS AND METHODS: Effects of morphine and M6S were studied across a range of pain modalities, using hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold (PPT) tests. KEY FINDINGS: Acutely, M6S was 3- to 5-fold more potent and 2- to 3-fold more efficacious than morphine in HPT and PST tests. No differences in analgesic drug potency/efficacy were detected in the PPT test. After 7-9days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all three pain tests. Furthermore, morphine-tolerant rats were not cross-tolerant to M6S. The selective δ-OR antagonist, naltrindole, blocked M6S-induced antinociception by 62±3% in the HPT test, 93±5% in the PST test, and 30±17% in the PPT test when examined acutely. SIGNIFICANCE: These studies provide additional confirmation for the mixed µ/δ activity of M6S and demonstrate potential improved clinical utility for dual µ/δ agonists relative to morphine in treatment of diabetic neuropathy across multiple pain domains.

Prevalence and incidence of urinary tract and genital infections among patients with and without type 2 diabetes.

OBJECTIVE: Epidemiological data on genitourinary infections (GUIs) comparing patients with and without type 2 diabetes (T2DM) is scant. We aimed to estimate the incidence of urinary tract infections (UTIs), genital infections (GIs), or any GUI in total and stratified by history of GUI and sex. RESEARCH DESIGN AND METHODS: We identified 39,295 patients in the Kaiser Permanente Northwest health plan with T2DM and an equal number of age and sex matched patients without diabetes. The cohort was followed for up to 9years (2006-2014). We calculated incidence rates and corresponding 95% confidence intervals (CI) of any GUI, UTIs and GIs adjusting for age, sex, race, BMI, presence of chronic kidney disease, annual number of outpatient visits, and diuretic use. RESULTS: Adjusted incidence of any GUI was 97.2/1000person-years (p-y) (95% CI 95.5-98.8) among the T2DM cohort vs. 79.7/1000 p-y (78.3-81.2) among those without diabetes. T2DM was associated with an adjusted 25% increased risk of UTI (rate ratio 1.25, 95% CI 1.22-1.29), a 26% increased risk of GI (1.26, 1.22-1.31) and a 22% increased risk of any GUI (1.22, 1.19-1.25). Incidence rates were lower among those with no GUI history, but the relative risks were similar. Women in both groups had higher incidence rates of GUIs than men. CONCLUSIONS: T2DM was associated with increased risks of any GUI, UTIs and GIs. Incidence rates of UTIs were higher than rates of GIs, but the relative risk of GIs was essentially identical. A similar pattern was observed when stratifying by sex. SIGNIFICANCE OF THE STUDY: RESEARCH QUESTIONS.

Treatment of Gabapentin Toxicity With Peritoneal Dialysis: Assessment of Gabapentin Clearance.

Gabapentin is almost exclusively cleared by the kidney and thus presents challenges in patients with kidney failure. Gabapentin is known to be effectively cleared by hemodialysis, but the efficiency of clearance by peritoneal dialysis (PD) has not been previously described. We report a case of gabapentin toxicity in a patient on long-term PD who was treated with continuous automated cycling PD. We find that continuous PD provides significant clearance of gabapentin. With 2-L exchanges every 2 hours, we document an apparent elimination half-life of 41.33 hours, which is substantially shorter than the reported elimination half-life of 132 hours in the absence of kidney function. Further, our patient's symptoms of gabapentin toxicity gradually improved and had fully resolved after about 36 hours of dialysis. Gabapentin clearance by PD was estimated at 94% of urea clearance. We conclude that intensive PD provides gabapentin clearance that approximates that of urea and is an effective but slow method to treat gabapentin overdose and toxicity.

The Prevalence and Management of Anemia in Chronic Kidney Disease Patients: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

Anemia is a common and significant complication of chronic kidney disease (CKD). However, its prevalence and current management status has not been studied thoroughly in Korea. We examined the prevalence of anemia, its association with clinical and laboratory factors, and utilization of iron agents and erythropoiesis stimulating agents using the baseline data from the large-scale CKD cohort in Korea. We defined anemia when hemoglobin level was lower than 13.0 g/dL in males and 12.0 g/dL in females, or received by erythropoiesis stimulating agents. Overall prevalence of anemia was 45.0% among 2,198 non-dialysis CKD patients from stage 1 to 5. Diabetic nephropathy (DN) as a cause, CKD stages, body mass index (BMI), smoking, leukocyte count, serum albumin, iron markers, calcium, and phosphorus concentration were identified as independent risk factors for anemia. Considering the current coverage of Korean National Health Insurance System, only 7.9% among applicable patients were managed by intravenous iron agents, and 42.7% were managed by erythropoiesis stimulating agents.

Predicting patient survival after deceased donor kidney transplantation using flexible parametric modelling.

BACKGROUND: The influence of donor and recipient factors on outcomes following kidney transplantation is commonly analysed using Cox regression models, but this approach is not useful for predicting long-term survival beyond observed data. We demonstrate the application of a flexible parametric approach to fit a model that can be extrapolated for the purpose of predicting mean patient survival. The primary motivation for this analysis is to develop a predictive model to estimate post-transplant survival based on individual patient characteristics to inform the design of alternative approaches to allocating deceased donor kidneys to those on the transplant waiting list in the United Kingdom. METHODS: We analysed data from over 12,000 recipients of deceased donor kidney or combined kidney and pancreas transplants between 2003 and 2012. We fitted a flexible parametric model incorporating restricted cubic splines to characterise the baseline hazard function and explored a range of covariates including recipient, donor and transplant-related factors. RESULTS: Multivariable analysis showed the risk of death increased with recipient and donor age, diabetic nephropathy as the recipient's primary renal diagnosis and donor hypertension. The risk of death was lower in female recipients, patients with polycystic kidney disease and recipients of pre-emptive transplants. The final model was used to extrapolate survival curves in order to calculate mean survival times for patients with specific characteristics. CONCLUSION: The use of flexible parametric modelling techniques allowed us to address some of the limitations of both the Cox regression approach and of standard parametric models when the goal is to predict long-term survival.

Ethnic disparities in risk of cardiovascular disease, end-stage renal disease and all-cause mortality: a prospective study among Asian people with Type 2 diabetes.

AIM: To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. METHODS: A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. RESULTS: Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; P<0.0001) and 1.60 (1.07-2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c , blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. CONCLUSIONS: Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities.

Relationship of urologic complications with health-related quality of life and perceived value of health in men and women with type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications (DCCT/EDIC) cohort.

OBJECTIVE: Limited information exists about the influence of urologic complications on health-related quality of life (HRQOL) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 664 men and 580 women from the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications Study: mean ages were 51.6 ± 6.6 and 50.6 ± 7.2 years and duration of diabetes was 29.5 ± 4.8 and 29.8 ± 5.1 years, respectively. We assessed associations of sexual dysfunction, lower urinary tract symptoms (LUTS), and, in women, urinary incontinence (UI) with general quality of life (SF-36), perceived value of health (EuroQol-5), diabetes-related quality of life (Diabetes Quality of Life Scale [DQOL]), and psychiatric symptoms (Symptom Checklist 90-R). RESULTS: In both men and women, urologic complications adversely affected HRQOL and psychiatric symptoms, even after accounting for history of depression leading to treatment. Multivariable analyses accounting for the presence of diabetic retinopathy, neuropathy, and nephropathy also revealed substantial independent effects. In men, for example, the odds (95% CI) of a low DQOL score (≤25th percentile) were 3.01 (1.90-4.75) times greater with erectile dysfunction and 2.65 (1.68-4.18) times greater with LUTS and in women, 2.04 (1.25-3.35) times greater with sexual dysfunction and 2.71 (1.72-4.27) times greater with UI/LUTS combined compared with men and women without such complications. Similar effects were observed for the other measures. CONCLUSIONS: Sexual dysfunction and urinary complications with type 1 diabetes are associated with decreased quality of life and perceived value of health and with higher levels of psychiatric symptoms, even after accounting for other diabetes complications and depression treatment.

[Actual cost of complex surgical treatment of patients with neuroischemic form of diabetic foot syndrome].

The results of calculation the average cost of complex surgical treatment of 52 patients with neuroischemic form of diabetic foot syndrome (Wagner 3, 4) are presented in the article. Calculation was performed in the program "Computer-aided system for calculation of patient's treatment cost" developed in A.V. Vishnevsky Institute of Surgery. This program permits you to analyze such components as hospital-stay duration, cost of surgery, pre- and postoperative management, pharmacotherapy, laboratory and instrumental research methods. Actual cost necessary to prevent high lower extremity amputations in patients with neuroischemic form of diabetic foot syndrome is 458 387.8 rubles per person that 10.02 times higher than amount allocated from the state budget.

Cost-effectiveness of hemodialysis in Japan.

Evaluation of the socioeconomic value of medical intervention and establishment of the resources necessary for clinical practice are important for continued development of the medical system. The purpose of this study was to investigate the cost-effectiveness of maintenance hemodialysis (MHD) for end-stage kidney disease in Japan. There were two aims: a socioeconomic evaluation of online hemodiafiltration (HDF) in the medical system and an analysis of MHD with respect to the primary diseases of chronic kidney disease. We performed a cost-effectiveness analysis based on quality-adjusted life years (QALY) and the incremental cost-effectiveness ratio (ICER). QALY were estimated using the EuroQOL-5 dimension. Reimbursement for medical fees in the national health insurance system was used as an indicator of costs. In a comparative analysis of hemodialysis and online HDF, a total of 288 dialysis interventions were observed for 4 weeks in 3 clinics. Among the subjects, nine patients were assigned to the HDF group. Consequently, the incremental cost-effectiveness ratio of HDF to hemodialysis was 20,589 ΔUSD/ΔQALY. In a comparative analysis of diabetic nephropathy and glomerulonephritis, seventeen patients (with a total of 243 dialysis sessions and a mean age of 63.2 ± 11.7 years) who underwent MHD for end-stage kidney disease (primary diseases: chronic glomerulonephritis [64.7%], diabetic nephropathy [35.3%]) were enrolled. After stratification for primary disease, the cost-effectiveness values for diabetic nephropathy were 88,774 ± 27,801 USD/QALY for 1 month and 97,416 ± 36,156 USD/QALY for 36 months. These results suggest that HDF is a cost-effective therapy. Additionally, the cost-effectiveness after 36 months of observation increased mainly among diabetic nephropathy patients.

Frailty and mortality in dialysis: evaluation of a clinical frailty scale.

BACKGROUND AND OBJECTIVES: Frailty is associated with poor outcomes for patients on dialysis; however, previous studies have not taken into account the severity of frailty as a predictor of outcomes. The purpose of this study was to assess if there was an association between the degree of frailty and mortality among patients on incident dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cohort study of incident chronic dialysis patients was conducted between January of 2009 and June of 2013 (last follow-up in December of 2013). On the basis of overall clinical impression, the Clinical Frailty Scale (CFS) score was determined for patients at the start of dialysis by their primary nephrologist. This simple scale allocates a single point to different states of frailty (1, very fit; 2, well; 3, managing well; 4, vulnerable; 5, mildly frail; 6, moderately frail; 7, severely frail or terminally ill) with an emphasis on function of the assessed individual. The primary outcome was time to death. Patients were censored at the time of transplantation. RESULTS: The cohort consisted of 390 patients with completed CFS scores (mean age of 63±15 years old). Most were Caucasian (89%) and men (67%), and 30% of patients had ESRD caused by diabetic nephropathy. The median Charlson Comorbidity Index score was 4 (interquartile range =3-6), and the median CFS score was 4 (interquartile range =2-5). There were 96 deaths over 750 patient-years at risk. In an adjusted Cox survival analysis, the hazard ratio associated with each 1-point increase in the CFS was 1.22 (95% confidence interval, 1.04 to 1.43; P=0.02). CONCLUSIONS: A higher severity of frailty (as defined by the CFS) at dialysis initiation is associated with higher mortality.

Coronary Artery Calcium Assessment in CKD: Utility in Cardiovascular Disease Risk Assessment and Treatment?

Coronary artery calcification (CAC) is a strong predictor of cardiovascular event rates in the general population, and scoring with multislice computed tomography commonly is used to improve risk stratification beyond clinical variables. CAC is accelerated in chronic kidney disease, but this occurs as a result of 2 distinct pathologic processes that result in medial (arteriosclerosis) and intimal (atherosclerosis) deposition. Although there are data that indicate that very high CAC scores may be associated with increased risk of death in hemodialysis, average CAC scores in most patients are elevated at a level at which discriminatory power may be reduced. There is a lack of data to guide management strategies in these patients based on CAC scores. There are even fewer data available for nondialysis patients, and it is uncertain whether CAC score confers an elevated risk of premature cardiovascular morbidity and mortality in such patients. In this article, we review the evidence regarding the utility of CAC score for noninvasive cardiovascular risk assessment in individuals with chronic kidney disease, using a clinical vignette that highlights some of the limitations in using CAC score and considerations in risk stratification.