Recovery of Renal Function among ESRD Patients in the US Medicare Program

Background

Patients started on long term hemodialysis have typically had low rates of reported renal recovery with recent estimates ranging from 0.9–2.4% while higher rates of recovery have been reported in cohorts with higher percentages of patients with acute renal failure requiring dialysis.

Study Design

Our analysis followed approximately 194,000 patients who were initiated on hemodialysis during a 2-year period (2008 & 2009) with CMS-2728 forms submitted to CMS by dialysis facilities, cross-referenced with patient record updates through the end of 2010, and tracked through December 2010 in the CMS SIMS registry.

Results

We report a sustained renal recovery (i.e no return to ESRD during the available follow up period) rate among Medicare ESRD patients of > 5% - much higher than previously reported. Recovery occurred primarily in the first 2 months post incident dialysis, and was more likely in cases with renal failure secondary to etiologies associated with acute kidney injury. Patients experiencing sustained recovery were markedly less likely than true long-term ESRD patients to have permanent vascular accesses in place at incident hemodialysis, while non-White patients, and patients with any prior nephrology care appeared to have significantly lower rates of renal recovery. We also found widespread geographic variation in the rates of renal recovery across the United States.

Conclusions

Renal recovery rates in the US Medicare ESRD program are higher than previously reported and appear to have significant geographic variation. Patients with diagnoses associated with acute kidney injury who are initiated on long-term hemodialysis have significantly higher rates of renal recovery than the general ESRD population and lower rates of permanent access placement.     

Circulating endoglin concentration is not elevated in chronic kidney disease

Background

Soluble endoglin, a TGF-β receptor, plays a key role in cardiovascular physiology. Whether circulating concentrations of soluble endoglin are elevated in CKD or underlie the high risk of cardiovascular death associated with chronic kidney disease (CKD) is unknown.

Methods

Individuals with and without CKD were recruited at a single center. Estimated glomerular filtration rate (eGFR) was estimated using the modified MDRD study equation and the serum creatinine at the time of recruitment, and patients were assigned to specific CKD stage according to usual guidelines. Serum endoglin concentration was measured by ELISA and univariate and multivariable regression was used to analyze the association between eGFR or CKD stage and the concentration of soluble endoglin.

Results

Serum endoglin was measured in 216 patients including 118 with stage 3 or higher CKD and 9 individuals with end stage renal disease (ESRD). Serum endoglin concentration did not vary significantly with CKD stage (increase of 0.16 ng/mL per 1 stage increase in CKD, P = 0.09) or eGFR (decrease -0.06 ng/mL per 10 mL/min/1.73 m² increase in GFR, P = 0.12), and was not higher in individuals with ESRD than in individuals with preserved renal function (4.2±1.1 and 4.3±1.2 ng/mL, respectively). Endoglin concentration was also not significantly associated with urinary albumin excretion.

Conclusions

Renal function is not associated with the circulating concentration of soluble endoglin. Elevations in soluble endoglin concentration are unlikely to contribute to the progression of CKD or the predisposition of individuals with CKD to develop cardiovascular disease.     

Maximising Acute Kidney Injury Alerts – A Cross-Sectional Comparison with the Clinical Diagnosis

Background

Acute kidney injury (AKI) is serious and widespread across healthcare (1 in 7 hospital admissions) but recognition is often delayed causing avoidable harm. Nationwide automated biochemistry alerts for AKI stages 1-3 have been introduced in England to improve recognition. We explored how these alerts compared with clinical diagnosis in different hospital settings.

Methods

We used a large population cohort of 4464 patients with renal impairment. Each patient had case-note review by a nephrologist, using RIFLE criteria to diagnose AKI and chronic kidney disease (CKD). We identified and staged AKI alerts using the new national NHS England AKI algorithm and compared this with nephrologist diagnosis across hospital settings.

Results

Of 4464 patients, 525 had RIFLE AKI, 449 had mild AKI, 2185 had CKD (without AKI) and 1305 were of uncertain chronicity. NHS AKI algorithm criteria alerted for 90.5% of RIFLE AKI, 72.4% of mild AKI, 34.1% of uncertain cases and 14.0% of patients who actually had CKD.The algorithm identified AKI particularly well in intensive care (95.5%) and nephrology (94.6%), but less well on surgical wards (86.4%). Restricting the algorithm to stage 2 and 3 alerts reduced the over-diagnosis of AKI in CKD patients from 14.0% to 2.1%, but missed or delayed alerts in two-thirds of RIFLE AKI patients.

Conclusion

Automated AKI detection performed well across hospital settings, but was less sensitive on surgical wards. Clinicians should be mindful that restricting alerts to stages 2-3 may identify fewer CKD patients, but including stage 1 provides more sensitive and timely alerting.     

WHO Antiretroviral Therapy Guidelines 2010 and Impact of Tenofovir on Chronic Kidney Disease in Vietnamese HIV-Infected Patients

Objective

The 2010 WHO antiretroviral therapy (ART) guidelines have resulted in increased tenofovir use. Little is known about tenofovir-induced chronic kidney disease (CKD) in HIV-infected Vietnamese with mean body weight of 55 kg. We evaluated the prevalence and risk factors of CKD in this country.

Design

Cross-sectional study was performed.

Methods

Clinical data on HIV-infected Vietnamese cohort were collected twice a year. To evaluate the prevalence of CKD, serum creatinine was measured in 771 patients in October 2011 and April 2012. CKD was defined as creatinine clearance less than 60 ml/min at both time points. Multivariate logistic regression was used to determine the factors associated with CKD

Results

Tenofovir use increased in Vietnam from 11.9% in April 2011 to 40.3% in April 2012. CKD was diagnosed in 7.3%, of which 7% was considered moderate and 0.3% was severe. Multivariate analysis of October-2011 data identified age per year-increase (OR: 1.229, 95%CI, 1.170-1.291), body weight per 1 kg-decrement (1.286, 1.193-1.386), and tenofovir use (2.715, 1.028-7.168) as risk factors for CKD.

Conclusions

Older age, low body weight and tenofovir use were independent risk factors for CKD in Vietnam. Further longitudinal study is required to evaluate the impact of TDF on renal function in Vietnam and other countries with small-body weight patients.     

Determining Glomerular Filtration Rate in Homozygous Sickle Cell Disease: Utility of Serum Creatinine Based Estimating Equations

Background

Various estimating equations have been developed to estimate glomerular filtration rate (GFR) for use in clinical practice. However, the unique renal physiological and pathological processes that occur in sickle cell disease (SCD) may invalidate these estimates in this patient population. This study aims to compare GFR estimated using common existing GFR predictive equations to actual measured GFR in persons with homozygous SCD. If the existing equations perform poorly, we propose to develop a new estimating equation for use in persons with SCD.

Methods

98 patients with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had serum measurements of creatinine, as well as had GFR measured using ^99mTc-DTPA nuclear renal scan. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and the serum creatinine based CKD-EPI equations. The Bland-Altman limit of agreement method was used to determine agreement between measured and estimated GFR values. A SCD-specific estimating equation for GFR (JSCCS-GFR equation) was generated by means of multiple regression via backward elimination.

Results

The mean measured GFR±SD was 94.9±27.4 mls/min/1.73 m² BSA, with a range of 6.4–159.0 mls/min/1.73 m². The MDRD and CG equations both overestimated GFR, with the agreement worsening with higher GFR values. The serum creatinine based CKD-EPI equation performed relatively well, but with a systematic bias of about 45 mls/min. The new equation developed resulted in a better fit to our sickle cell disease data than the MDRD equation.

Conclusion

Current estimating equations, other than the CKD-EPI equation, do not perform very accurately in persons with homozygous SS disease. A fairly accurate estimating equation, suitable for persons with GFR >60 mls/min/1.73 m² has been developed from our dataset and validated within a simulated dataset.     

Pre-Dialysis Visits to a Nephrology Department and Major Cardiovascular Events in Patients Undergoing Dialysis

Background and Objectives

Pre-dialysis care by a nephrology out-patient department (OPD) may affect the outcomes of patients who ultimately undergo maintenance dialysis. This study examined the effect of pre-dialysis care by a nephrology OPD on the incidence of one-year major cardiovascular events after initiation of dialysis.

Design, Setting Participants, & Measurements

The study consisted of Taiwanese patients with chronic kidney disease (CKD) who commenced dialysis from 2006 to 2008. The number of nephrology OPD visits during the critical care period (within 6 months of initiation of dialysis) and the early care period (6–36 months before initiation of dialysis) were analyzed. The primary outcome measure was one-year major cardiovascular events.

Results

A total of 1191 CKD patients who initiated dialysis from 2006 to 2008 were included. Binary logistic regression showed that patients with ≧3 visits during the critical care period and those with ≧11 visits during the early care period had fewer composite major cardiovascular events than those with 0 visits. Patients with early referral are less likely to experience composite major cardiovascular events than those with late referral, with aOR 0.574 (95% CI = 0.43–0.77, P<0.001). Patients with both ≧3 visits during critical care period and ≧11 visits during early care period were less likely to experience composite major cardiovascular events (aOR = 0.25, 95% CI = 0.16–0.39, P < 0.001).

Conclusions

Patients with adequate pre-dialysis nephrology OPD visits, not just early referral, may had fewer one-year composite major cardiovascular events after initiation of dialysis. This information may be important to medical care providers and public health policy makers in their efforts to improve the well-being of CKD patients.     

Cardiac Troponin I in Non- Acute Coronary Syndrome Patients with Chronic Kidney Disease

Objective

The aim of this study was to assess the results of troponin I (cTnI) in non- acute Coronary Syndrome (ACS) patients with chronic kidney disease (CKD). We also examined the risk factors for elevated cTnI in non-ACS patients with CKD and whether stage 5 CKD modifies the associations of elevated cTnI and the risk factors in non-ACS patients with CKD.

Methods

A retrospective study was performed. Logistic regression models were used.

Results

293 non-ACS patients with CKD were included in the current study. 43.34% non-ACS patients with CKD have an elevated cTnI level and 5.12% have an elevated cTnT level in MI range. In CKD patients without ACS and heart failure, only 26.03% (38/146) patients have an elevated cTnT level. In adjusted analyses, age, diastolic blood pressure and congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD. Congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD (OR 2.30, 95% CI 1.08,4.88, P=0.03). Stage 5 CKD does not modify the association of congestive heart failure and an elevated cTnI level.

Conclusion

43.34% non-ACS patients with CKD and 26.03% CKD patients without ACS and congestive heart failure have an elevated cTnI level. Congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD. Stage 5 CKD does not modify the association of congestive heart failure and an elevated cTnI level.     

Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphism and Left Ventricular Function in Early Chronic Kidney Disease

Background

Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.

Methods

140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.

Results

The median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively).

Conclusions

eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.     

Subjective Motives for Requesting In-Patient Treatment in Female with Anorexia Nervosa: A Qualitative Study

Background

Anorexia nervosa is a severe psychiatric disorder mainly affecting women. Its treatment is long and accepted with much difficulty, in particular in-patient treatment.

Aims

To describe the subjective motives of women with anorexia nervosa for requesting in-patient admission, from a qualitative analysis of application letters.

Methods

Participants were adult women (18 years and older) with anorexia nervosa who were admitted as in-patients in a referral hospital unit in France from January 2008 to December 2010. The application letters, prerequisites to admission, were studied by the interpretative phenomenological method of content analysis.

Results

63 letters have been analysed, allowing the identification of six themes related to requests for in-patient care: loss of control of behaviour, and of thoughts, mental exhaustion, isolation, inner struggle and fear of recovery.

Conclusions

Requests for in-patient admission were motivated by very personal, subjective experiences, unrelated to medical reasons for admission. These results may help improve pre-admission motivational work with individuals, by basing it on their subjective experience.     

Post-Bypass Dexmedetomidine Use and Postoperative Acute Kidney Injury in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

Background

And Objectives: The aim of this retrospective investigation was to study the relationships among chronic kidney disease, acute kidney injury (AKI), and potential benefits by post-bypass dexmedetomidine use in patients undergoing cardiac surgery.

Methods

The patient data were reviewed from the institutional Society of Thoracic Surgeons National Adult Cardiac Surgery Database after IRB approval. 1,133 patients were identified and divided into two groups: those who received dexmedetomidine or those who did not during the post-bypass period. The postoperative outcomes include the incidence of AKI, any complication and all cause of mortality.

Results

Post-bypass dexmedetomidine use was associated with significantly reduced the incidence of total AKI (26.1% vs. 33.75%; adjusted OR, 0.7033; 95%CI, 0.540 to 0.916; p=0.0089). In addition, post-bypass dexmedetomidine use was more likely to reduce the incidence of AKI in these patients with preoperative normal kidney function (Stage1; 32.8% to 22.8%; p=0.0233) and mild CKD (Stage 2; 32.8% to 24.7; p=0.0003) after cardiac surgery. Post-bypass infusion of dexmedetomidine was associated with significantly reduced incidence of any complication and 30-day mortalities.

Conclusions

Post-bypass dexmedetomidine use is associated with a significant reduction in the incidence of AKI, especially mild AKI in patients with preoperative normal renal function and mild CKD undergoing cardiac surgery.     

Association of High-Density Lipoprotein Cholesterol with the Estimated Glomerular Filtration Rate in a Community-Based Population

Background

Reduced kidney function is independently associated with low high-density lipoprotein cholesterol (HDL-C) levels in patients with end-stage renal disease (ESRD), those on hemodialysis, and those with stage 3–5 chronic kidney disease (CKD). However, epidemiological data investigating the relationship between HDL-C levels and kidney function in the general population with roughly normal kidney function are limited, and the results are also inconsistent. The aim of this study was to evaluate the relationship between HDL-C levels and the estimated glomerular filtration rate (eGFR) in a community-based population in China.

Methods

This was a community-based cross-sectional survey. In total, 4925 participants (age range, 18–96 years; mean, 51.30±11.98 years) were recruited during routine health status examinations. A questionnaire was used to ascertain age, smoking status, and the history of hypertension and diabetes mellitus for each participant. We measured the body mass index, waist circumference, systolic and diastolic blood pressure, and fasting glucose, total cholesterol, triglyceride, HDL-C, low-density lipoprotein cholesterol, uric acid, and serum creatinine level of each participant. eGFR was evaluated using the Chinese modified Modification of Diet in Renal Disease equation.

Results

The HDL-C level was higher in the first quartile (lowest quartile) of eGFR than in the fourth quartile (the highest quartile). Additionally, HDL-C levels decreased as eGFR decreased. Pearson’s correlation analysis revealed that HDL-C levels were associated with eGFR (r=0.16). After adjustment for some confounders, HDL-C was independently associated with all quartiles of eGFR in the participants.

Conclusions

HDL-C was independently associated with kidney function in a community-dwelling general population. The association between low HDL-C levels and a decreased eGFR gradually strengthened as eGFR declined.     

Estimated Glomerular Filtration Rate,All-Cause Mortality and Cardiovascular Diseases Incidence in a Low Risk Population: The MATISS Study

Background

Chronic kidney disease (CKD) independently increases the risk of death and cardiovascular disease (CVD) in the general population. However, the relationship between estimated glomerular filtration rate (eGFR) and CVD/death risk in a general population at low risk of CVD has not been explored so far.

Design

Baseline and longitudinal data of 1465 men and 1459 women aged 35-74 years participating to the MATISS study, an Italian general population cohort, were used to evaluate the role of eGFR in the prediction of all-cause mortality and incident CVD.

Methods

Bio-bank stored sera were used to evaluate eGFR at baseline. Serum creatinine was measured on thawed samples by means of an IDMS-calibrated enzymatic method. eGFR was calculated by the CKD-EPI formula.

Results

At baseline, less than 2% of enrolled persons had eGFR < 60 mL/min/1.73m² and more than 70% had a 10-year cardiovascular risk score < 10%. In people 60 or more years old, the first and the last eGFR quintiles (<90 and ≥109 mL/min/1.73m², respectively) were associated to an increased risk for both all-cause mortality (hazard ratio 1.6, 95% confidence interval 1.2-2.1 and 4.3, 1.6-11.7, respectively) and incident CVD (1.6, 1.0-2.4 and 7.0, 2.2-22.9, respectively), even if adjusted for classical risk factors.

Conclusions

These findings strongly suggest that in an elderly, general population at low risk of CVD and low prevalence of reduced renal filtration, even a modest eGFR reduction is related to all-cause mortality and CVD incidence, underlying the potential benefit to this population of considering eGFR for their risk prediction.     

Apolipoprotein E Gene Variants on the Risk of End Stage Renal Disease

Objective

End-stage renal disease (ESRD) is a severe health concern over the world. Associations between apolipoprotein E (apoE) gene polymorphisms and the risk of ESRD remained inconclusive. This study aimed to investigate the association between apoE gene polymorphisms and ESRD susceptibility.

Methods

Databases including PubMed, Embase, Web of Science and the Cochrane Library were searched to find relevant studies. Meta-analysis method was used synthesize the eligible studies.

Results

Sixteen pertinent case-control studies which included 3510 cases and 13924 controls were analyzed. A significant association was found between ε2 allele and the ESRD risk (odds ratio (OR) = 1.30, 95% confidence interval (CI) 1.15–1.46, P < 0.0001; I ² = 18%, P for heterogeneity = 0.24). The ε2ε3, ε2ε4, ε3ε3, ε3ε4, ε4ε4, ε3 and ε4 were not associated with the susceptibility of ESRD. In the subgroup analysis by ethnicity, there was a statistically significant association between ε2ε3 or ε2 allele and ESRD risk in East Asians (OR = 1.66, 95% CI 1.31–2.10, P < 0.0001; OR = 1.62, 95% CI 1.31–2.01, P < 0.0001, respectively), but not in Caucasians. E2 carriers had higher plasma apoE (mean difference = 16.24 mg/L, 95% CI 7.76-24.73, P = 0.0002) than the (ε3 + ε4) carriers in patients with ESRD. The publication bias was not significant.

Conclusion

The ε2 allele of apoE gene might increase the risk of ESRD. E2 carriers expressed higher level of plasma apoE in patients with ESRD. More well-designed studies are needed to confirm these associations in the future.     

Incident Chronic Kidney Disease and Newly Developed Complications Related to Renal Dysfunction in an Elderly Population during 5 Years: A Community-Based Elderly Population Cohort Study

Background

Few studies have evaluated the association between incident chronic kidney disease (CKD) and related complications, especially in elderly population. We attempted to verify the association between GFR and concurrent CKD complications and elucidate the temporal relationship between incident CKD and new CKD complications in a community-based prospective elderly cohort.

Method

We analyzed the available data from 984 participants in the Korean Longitudinal Study on Health and Aging. Participants were categorized into 6 groups according to eGFR at baseline examination (≥90, 75–89, 60–74, 45–59, 30–44, and <30 ml/min/1.73 m²).

Result

The mean age of study population was 76 ± 9.1 years and mean eGFR was 72.3 ± 17.0 ml/min/1.73 m². Compared to eGFR group 1, the odds ratio (OR) for hypertension was 2.363 (95% CI, 1.299-4.298) in group 4, 5.191 (2.074-12.995) in group 5, and 13.675 (1.611-115.806) in group 6; for anemia, 7.842 (2.265-27.153) in group 5 and 13.019 (2.920-58.047) in group 6; for acidosis, 69.580 (6.770-715.147) in group 6; and for hyperkalemia, 19.177 (1.798-204.474) in group 6. Over a 5-year observational period, CKD developed in 34 (9.6%) among 354 participants with GFR ≥ 60 ml/min/1.73 m² at basal examination. The estimated mean number of new complications according to analysis of co-variance was 0.52 (95% CI, 0.35–0.68) in subjects with incident CKD and 0.24 (0.19–0.29) in subjects without CKD (p = 0.002). Subjects with incident CKD had a 2.792-fold higher risk of developing new CKD complications. A GFR level of 52.4 ml/min/1.73 m² (p = 0.032) predicted the development of a new CKD complication with a 90% sensitivity.

Conclusion

In an elderly prospective cohort, CKD diagnosed by current criteria is related to an increase in the number of concurrent CKD complications and the development of new CKD complications.     

Prevalence of chronic kidney disease and progression of disease over time among patients enrolled in the Houston West Nile virus cohort

Introduction

In experimental models of West Nile virus (WNV) infection, animals develop chronic kidney infection with histopathological changes in the kidney up to 8-months post-infection. However, the long term pathologic effects of acute infection in humans are largely unknown. The purpose of this study was to assess renal outcomes following WNV infection, specifically the development of chronic kidney disease (CKD).

Methods

In a cohort of 139 study participants with a previous diagnosis of WNV infection, we investigated the prevalence of CKD using the Kidney Disease Outcomes Quality Initiative (KDOQI) criteria based on the Modification of Diet in Renal Disease (MDRD) formula and urinary abnormalities, and assessed various risk factors and biomarkers.

Results

Study participants were primarily male (60%) and non-Hispanic white (86%) with a mean age of 57 years. Most (83%) were four to nine years post-infection at the time of this study. Based on the KDOQI definition, 40% of participants had evidence of CKD, with 10% having Stage III or greater and 30% having Stage I–II. By urinary dipstick testing, 26% of patients had proteinuria and 23% had hematuria. Plasma NGAL levels were elevated in 14% of participants while MCP-1 levels were increased in 12%. Over 1.5 years, the average change in eGFR was −3.71 mL/min/1.73 m². Only a history of Neuroinvasive WNV disease was independently associated with CKD following multivariate analysis.

Discussion

We found a high prevalence of CKD after long term follow-up in a cohort of participants previously infected with WNV. The majority of those with CKD are in Stage I-II indicating early stages of renal disease. Traditional risk factors were not associated with the presence of CKD in this population. Therefore, clinicians should regularly evaluate all patients with a history of WNV for evidence of CKD.     

Association of Individual Non-Steroidal Anti-Inflammatory Drugs and Chronic Kidney Disease: A Population-Based Case Control Study

Background

Non-steroidal anti-inflammatory agents (NSAIDs) are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD), specifically, across various NSAIDs.

Aim

The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.

Methods

A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID). Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID), with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.

Results

Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44) and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44), meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87) and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21).

Conclusions

The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.     

Comparative Effectiveness of Cognitive Therapies Delivered Face-to-Face or over the Telephone: An Observational Study Using Propensity Methods

Objectives

To compare the clinical and cost-effectiveness of face-to-face (FTF) with over-the-telephone (OTT) delivery of low intensity cognitive behavioural therapy.

Design

Observational study following SROBE guidelines. Selection effects were controlled using propensity scores. Non-inferiority comparisons assessed effectiveness.

Setting

IAPT (improving access to psychological therapies) services in the East of England.

Participants

39,227 adults referred to IAPT services. Propensity score strata included 4,106 individuals; 147 pairs participated in 1∶1 matching.

Intervention

Two or more sessions of computerised cognitive behavioural therapy (CBT).

Main outcome measures

Patient-reported outcomes: Patient Health Questionnaire (PHQ-9) for depression; Generalised Anxiety Disorder questionnaire (GAD-7); Work and Social Adjustment Scale (WSAS). Differences between groups were summarised as standardised effect sizes (ES), adjusted mean differences and minimally important difference for PHQ-9. Cost per session for OTT was compared with FTF.

Results

Analysis of covariance controlling for number of assessments, provider site, and baseline PHQ-9, GAD-7 and WSAS indicated statistically significantly greater reductions in scores for OTT treatment with moderate (PHQ-9: ES: 0.14; GAD-7: ES: 0.10) or small (WSAS: ES: 0.03) effect sizes. Non-inferiority in favour of OTT treatment for symptom severity persisted as small to moderate effects for all but individuals with the highest symptom severity. In the most stringent comparison, the one-to-one propensity matching, adjusted mean differences in treatment outcomes indicated non-inferiority between OTT versus FTF treatments for PHQ-9 and GAD-7, whereas the evidence was moderate for WSAS. The per-session cost for OTT was 36.2% lower than FTF.

Conclusions

The clinical effectiveness of low intensity CBT-based interventions delivered OTT was not inferior to those delivered FTF except for people with more severe illness where FTF was superior. This provides evidence for better targeting of therapy, efficiencies for patients, cost savings for services and greater access to psychological therapies for people with common mental disorders.     

Hypokalemia,Its Contributing Factors and Renal Outcomes in Patients with Chronic Kidney Disease

Background

In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated.

Design, Participants & Measurements

2500 participants with CKD stage 1–4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used.

Results

The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m². Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03–3.22) in sK <3.5mEq/L and 1.67 (95% CI,1.19–2.35) in sK = 3.5–4 mEq/L, respectively, compared with sK = 4.5–5 mEq/L. Hyperkalemia defined as sK >5 mEq/L conferred 1.6-fold (95% CI,1.09–2.34) increased risk of ESRD compared with sK = 4.5–5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range.

Conclusion

In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.     

A Cross-Sectional Randomised Study of Fracture Risk in People with HIV Infection in the Probono 1 Study

Objective

To determine comparative fracture risk in HIV patients compared with uninfected controls.

Design

A randomised cross-sectional study assessing bone mineral density (BMD), fracture history and risk factors in the 2 groups.

Setting

Hospital Outpatients.

Subbbjects

222 HIV infected patients and an equal number of age-matched controls. Assessments: Fracture risk factors were assessed and biochemical, endocrine and bone markers measured. BMD was assessed at hip and spine. 10-year fracture probability (FRAX) and remaining lifetime fracture probability (RFLP) were calculated.

Main Outcome Measures

BMD, and history of fractures.

Results

Reported fractures occurred more frequently in HIV than controls, (45 vs. 16; 20.3 vs. 7%; OR=3.27; p=0.0001), and unsurprisingly in this age range, non-fragility fractures in men substantially contributed to this increase. Osteoporosis was more prevalent in patients with HIV (17.6% vs. 3.6%, p<0.0001). BMD was most reduced, and predicted fracture rates most increased, at the spine. Low BMD was associated with antiretroviral therapy (ART), low body mass index and PTH. 10-year FRAX risk was <5% for all groups. RLFP was greater in patients with HIV (OR=1.22; p=0.003) and increased with ART (2.4 vs. 1.50; OR= 1.50; p=0.03).

Conclusions

The increased fracture rate in HIV patients in our relatively youthful population is partly driven by fractures, including non-fragility fractures, in men. Nonetheless, these findings may herald a rise in osteoporotic fractures in HIV patients. An appropriate screening and management response is required to assess these risks and identify associated lifestyle factors that are also associated with other conditions such as cardiovascular disease and diabetes.     

Pancreatic Endocrine and Exocrine Function in Children following Near-Total Pancreatectomy for Diffuse Congenital Hyperinsulinism

Context

Congenital hyperinsulinism (CHI), the commonest cause of persistent hypoglycaemia, has two main histological subtypes: diffuse and focal. Diffuse CHI, if medically unresponsive, is managed with near-total pancreatectomy. Post-pancreatectomy, in addition to persistent hypoglycaemia, there is a very high risk of diabetes mellitus and pancreatic exocrine insufficiency.

Setting

International referral centre for the management of CHI.

Patients

Medically unresponsive diffuse CHI patients managed with near-total pancreatectomy between 1994 and 2012.

Intervention

Near-total pancreatectomy.

Main Outcome Measures

Persistent hypoglycaemia post near-total pancreatectomy, insulin-dependent diabetes mellitus, clinical and biochemical (faecal elastase 1) pancreatic exocrine insufficiency.

Results

Of more than 300 patients with CHI managed during this time period, 45 children had medically unresponsive diffuse disease and were managed with near-total pancreatectomy. After near-total pancreatectomy, 60% of children had persistent hypoglycaemia requiring medical interventions. The incidence of insulin dependent diabetes mellitus was 96% at 11 years after surgery. Thirty-two patients (72%) had biochemical evidence of severe pancreatic exocrine insufficiency (Faecal elastase 1<100 µg/g). Clinical exocrine insufficiency was observed in 22 (49%) patients. No statistically significant difference in weight and height standard deviation score (SDS) was found between untreated subclinical pancreatic exocrine insufficiency patients and treated clinical pancreatic exocrine insufficiency patients.

Conclusions

The outcome of diffuse CHI patients after near-total pancreatectomy is very unsatisfactory. The incidence of persistent hypoglycaemia and insulin-dependent diabetes mellitus is very high. The presence of clinical rather than biochemical pancreatic exocrine insufficiency should inform decisions about pancreatic enzyme supplementation.