GlycA,a marker of protein glycosylation,is related to albuminuria and estimated glomerular filtration rate: the ELSA-Brasil study

Background

Systemic inflammation has been implicated in several chronic diseases. GlycA is a new nuclear mass resonance (NMR) spectroscopy-derived biomarker of systemic inflammation that reflects protein glycosylation. We evaluated the association of GlycA with albuminuria and eGFR in the ELSA-Brasil Study.

Methods

The cross-sectional association between GlycA (automated NMR LipoProfile(®) test spectra, LabCorp, Raleigh, NC), and overnight 12 h–albuminuria and CKD-EPI eGFR was evaluated among 5050 participants.

Results

GlycA was higher among older, women, smokers, alcohol abstemious, obese and in those with diabetes, hypertension or dyslipidemia. In addition, both eGFR and albuminuria were associated to GlycA. In linear regression, GlycA was independently associated with log albuminuria (B 0.03; 95%CI 0.02–0.04, P?<?0.0001, per 1sd increase) and inversely related to eGFR (B -0.53; 95%CI -0.99 – -0.07, P?<?0.02), even after adjustments including hsCRP. In logistic regression, GlycA was independently related to the risk of A2 or A3 albuminuria (OR 1.42, 95%CI 1.27–1.57, p?<?0.0001, per 1sd increase), of having an eGFR?<?60 ml/min/1.73m² (OR 1.26, 95%CI 1.12–1.41, p?=?0.0003, per 1 sd) or of a combined diagnosis of both conditions (OR 1.35, 95%CI 1.23–1.46, p?<?0.0001, per 1 sd). In the ROC curve, GlycA had a higher AUC in comparison to hsCRP (AUC 0.67 vs. 0.62, p?=?0.06) for the association with albuminuria A2 or A3.

Conclusions

The present study demonstrates that GlycA is associated with albuminuria and eGFR, independently of major risk factors for CKD progression, including (and with a stronger association than) hsCRP. GlycA should be further evaluated in CKD progression.

     

Mortality Associated with Metformin Versus Sulfonylurea Initiation: A Cohort Study of Veterans with Diabetes and Chronic Kidney Disease

Background

For patients with type 2 diabetes and chronic kidney disease (CKD), high-quality evidence about the relative benefits and harms of oral glucose-lowering drugs is limited.

Objective

To evaluate whether mortality risk differs after the initiation of monotherapy with either metformin or a sulfonylurea in Veterans with type 2 diabetes and CKD.

Design

Observational, national cohort study in the Veterans Health Administration (VHA).

Participants

Veterans who received care from the VHA for at least 1 year prior to initiating monotherapy treatment for type 2 diabetes with either metformin or a sulfonylurea between 2004 and 2009.

Main Measures

Metformin and sulfonylurea use was assessed from VHA electronic pharmacy records. The CKD-EPI equation was used to estimate glomerular filtration rate (eGFR). The outcome of death from January 1, 2004, through December 31, 2009, was assessed from VHA Vital Status files.

Key Results

Among 175,296 new users of metformin or a sulfonylurea monotherapy, 5121 deaths were observed. In primary analyses adjusted for all measured potential confounding factors, metformin monotherapy was associated with a lower mortality hazard ratio (HR) compared with sulfonylurea monotherapy across all ranges of eGFR evaluated (HR ranging from 0.59 to 0.80). A secondary analysis of mortality risk differences favored metformin across all eGFR ranges; the greatest risk difference was observed in the eGFR category 30–44 mL/min/1.73m² (12.1 fewer deaths/1000 person-years, 95% CI 5.2–19.0).

Conclusions

Initiation of metformin versus a sulfonylurea among individuals with type 2 diabetes and CKD was associated with a substantial reduction in mortality, in terms of both relative and absolute risk reduction. The largest absolute risk reduction was observed among individuals with moderately–severely reduced eGFR (30–44 mL/min/1.73m²).

     

Hypertension and the development of New onset chronic kidney disease over a 10 year period: a retrospective cohort study in a primary care setting in Malaysia

Background

Little is known about the rate of progression to chronic kidney disease (CKD) among hypertensive patients, particularly at the primary care level. This study aims to examine risk factors associated with new onset CKD among hypertensive patients attending a primary care clinic.

Methods

This is a 10-year retrospective cohort study of 460 patients with hypertension who were on treatment. Patient information was collected from patient records. CKD was defined as a glomerular filtration rate <60?ml/min per 1.73?m² (Cockcroft-Gault equation). Multiple logistic regression statistics was used to test the association in newly diagnosed CKD.

Results

The incidence of new CKD was 30.9% (n?=?142) with an annual rate of 3%. In multivariate logistic regression analysis, factors associated with development of new onset of CKD among hypertensive patients were older age (odds ratio [OR] 1.123, 95% confidence interval [CI] 1.078-1.169), presence of diabetes (OR 2.621, 95% CI 1.490-4.608), lower baseline eGFR (OR 1.041, 95% CI 0.943-0.979) and baseline hyperuricaemia (OR 1.004, 95% CI 1.001-1.007).

Conclusions

The progression to new onset CKD is high among urban multiethnic hypertensive patients in a primary care population. Hence every effort is needed to detect the presence of new onset CKD earlier. Hypertensive patients who are older, with underlying diabetes, hyperuricaemia and lower baseline eGFR are associated with the development of CKD in this population.

     

Comparison of equations for estimating glomerular filtration rate in screening for chronic kidney disease in asymptomatic black Africans: a cross sectional study

Background

Several equations have been developed to estimate glomerular filtration rate (eGFR). The common equations used were derived from populations predominantly comprised of Caucasians with chronic kidney disease (CKD). Some of the equations provide a correction factor for African-Americans due to their relatively increased muscle mass and this has been extrapolated to black Africans. Studies carried out in Africa in patients with CKD suggest that using this correction factor for the black African race may not be appropriate. However, these studies were not carried out in healthy individuals and as such the extrapolation of the findings to an asymptomatic black African population is questionable. We sought to compare the proportion of asymptomatic black Africans reported as having reduced eGFR using various eGFR equations. We further compared the association between known risk factors for CKD with eGFR determined using the different equations.

Methods

We used participant and laboratory data collected as part of a global reference interval study conducted by the Committee of Reference Intervals and Decision Limits (C-RIDL) under the International Federation of Clinical Chemistry (IFCC). Serum creatinine values were used to calculate eGFR using the Cockcroft-Gault (CG), re-expressed 4 variable modified diet in renal disease (4v–MDRD), full age spectrum (FAS) and chronic kidney disease epidemiology collaboration equations (CKD-EPI). CKD classification based on eGFR was determined for every participant.

Results

A total of 533 participants were included comprising 273 (51.2%) females. The 4v–MDRD equation without correction for race classified the least number of participants (61.7%) as having an eGFR equivalent to CKD stage G1 compared to 93.6% for CKD-EPI with correction for race. Only age had a statistically significant linear association with eGFR across all equations after performing multiple regression analysis. The multiple correlation coefficients for CKD risk factors were higher for CKD-EPI determined eGFRs.

Conclusions

This study found that eGFR determined using CKD-EPI equations better correlated with a prediction model that included risk factors for CKD and classified fewer asymptomatic black Africans as having a reduced eGFR compared to 4v–MDRD, FAS and CG corrected for body surface area.

     

Treatment of Hypertension in Chronic Kidney Disease

Purpose of Review

Chronic kidney disease (CKD) is recognized as a worldwide epidemic. Hypertension commonly coexists with CKD and its prevalence is progressively increasing as kidney function declines.

Recent Findings

For patients with established CKD and/or diabetes with albuminuria, the updated hypertension guidelines have recommended a blood pressure (BP) goal <?130/80 mmHg. Blood pressure level above 130/80 mmHg in CKD patients requires lifestyle modifications and multiple antihypertensive medications. According to recent guidelines, angiotensin-converting enzyme (ACE) inhibitors should be the drugs of first choice. Angiotensin II receptor blockers (ARBs) should be used if the ACE inhibitor is not tolerated. Non-dihydropyridine CCBs consistently reduce albuminuria and slow the decline in kidney function. Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. Diuretics are commonly used and represent the cornerstone in the management of CKD patients. All the other agents are used when treatment with the other primary agents have failed.

Summary

In patients with CKD, an intensive BP goal <?130/80 mmHg has been recommended. We review current treatment options.

     

Urinary mitochondrial DNA level as a biomarker of tissue injury in non-diabetic chronic kidney diseases

Background

Urinary mitochondrial DNA (mtDNA) fragment level has been proposed as a biomarker of chronic kidney disease (CKD). In this study, we determine the relation between urinary mtDNA level and rate of renal function deterioration in non-diabetic CKD.

Methods

We recruited 102 non-diabetic CKD patients (43 with kidney biopsy that showed non-specific nephrosclerosis). Urinary mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 48.3?±?31.8?months for renal events (need of dialysis or over 30% reduction in estimated glomerular filtration rate [eGFR]).

Results

The median urinary mtDNA level was 1519.42 (inter-quartile range 511.81–3073.03) million copy/mmol creatinine. There were significant correlations between urinary mtDNA level and baseline eGFR (r?=?0.429, p?<?0.001), proteinuria (r?=?0.368, p?<?0.001), severity of glomerulosclerosis (r?=???0.537, p?<?0.001), and tubulointerstitial fibrosis (r?=???0.374, p?=?0.014). The overall rate of eGFR decline was ??2.18?±?5.94?ml/min/1.73m² per year. There was no significant correlation between the rate of eGFR decline and urinary mtDNA level. By univariate analysis, urinary mtDNA level predicts dialysis-free survival, but the result became insignificant after adjusting for clinical and histological confounding factors.

Conclusion

Urinary mtDNA levels have no significant association with the rate of renal function decline in non-diabetic CKD, although the levels correlate with baseline renal function, proteinuria, and the severity of histological damage. Urinary mtDNA level may be a surrogate marker of permanent renal damage in non-diabetic CKD.

     

Aspirin for Primary Prevention of Cardiovascular Disease and Renal Disease Progression in Chronic Kidney Disease Patients: a Multicenter Randomized Clinical Trial (AASER Study)

Background

Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular events. However, limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression.

Study Design

Prospective, multicenter, open-label randomized controlled trial.

Setting and Participants

One hundred eleven patients with estimated glomerular filtration rate (eGFR) 15–60 ml/min/1.73 m² without previous cardiovascular events.

Intervention

Aspirin treatment (100 mg/day) (n?=?50) or usual therapy (n?=?61). Mean follow-up time was 64.8?±?16.4 months.

Outcomes

The primary endpoint was composed of cardiovascular death, acute coronary syndrome (nonfatal MI, coronary revascularization, or unstable angina pectoris), cerebrovascular disease, heart failure, or nonfatal peripheral arterial disease. Secondary endpoints were fatal and nonfatal coronary events, renal events (defined as doubling of serum creatinine, ≥?50% decrease in eGFR, or renal replacement therapy), and bleeding episodes.

Results

During follow-up, 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups, respectively. Aspirin did not significantly reduce primary composite endpoint (HR, 0.396 (0.146–1.076), p?=?0.069. Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group. Aspirin significantly reduced the risk of coronary events (log-rank, 5.997; p?=?0.014). Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group. Aspirin treatment decreased renal disease progression in a model adjusted for age, baseline kidney function, and diabetes mellitus (HR, 0.272; 95% CI, 0.077–0.955; p?=?0.043) but did not when adjusted for albuminuria. No differences were found in minor bleeding episodes between groups and no major bleeding was registered.

Limitations

Small sample size and open-label trial.

Conclusions

Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint; however, there were reductions in secondary endpoints with fewer coronary events and renal outcomes. ClinicalTrials.gov Identifier: NCT01709994.

     

Chronic kidney disease and underdiagnosis of renal insufficiency among diabetic patients attending a hospital in Southern Ethiopia

Background

Diabetic patients with chronic kidney disease (CKD), as defined by a reduced glomerular filtration rate (GFR), are at greater risk for cardiovascular and renal events and mortality. The aim of this study was to determine the prevalence of CKD among diabetic patients attending a hospital in southern Ethiopia, and to assess underdiagnosis of renal insufficiency among those with normal serum creatinine.

Methods

A total of 214 randomly selected diabetics attending the follow-up clinic at Butajira hospital of southern Ethiopia participated in this study during the period from September 1 to October 31, 2013. All patients completed an interviewer-administered questionnaire and underwent clinical assessment. The simplified Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault (C-G) equations were used to estimate GFR (eGFR) from serum creatinine.

Results

CKD, defined as eGFR?<?60 ml/min/1.73 m², was present in 18.2% and 23.8% of the study participants according to the MDRD and Cockcroft-Gault (C-G) equations, respectively. Only 9.8% of the total participants, and 48.7% (for the MDRD) and 37.3% (for C-G) of those with eGFR <60 ml/min/1.73 m² had abnormal serum creatinine values, i.e. > 1.5 mg/dl. Normal serum creatinine was observed in 90.2% of participants attending the hospital. A large proportion of participants ranging from 38.9-56.5% have shown to have mild to moderate renal insufficiency (stage 2–3 CKD) despite normal creatinine levels. CKD, eGFR?<?60 ml/min/1.73 m², was found in 10.4 and 16.9% of participants with normal serum creatinine using the MDRD and C-G equations, respectively.

Conclusion

CKD is present in no less than 18% of diabetics attending the hospital, but it is usually undiagnosed. A significant number of diabetics have renal insufficiency corresponding to stages 2–3 CKD despite normal creatinine levels. Therefore, GFR should be considered as an estimate of renal insufficiency, regardless of serum creatinine levels being in normal range.

     

Autosomal-dominante polyzystische Nierenerkrankung

Background

Patients with autosomal dominant polycystic kidney disease (ADPKD) have a varying risk for progression to renal failure and the necessity for dialysis depending on the individual risk profile. This review summarizes the current knowledge on the genetics and pathophysiology relevant for individual disease progression and currently available treatment strategies for ADPKD are assessed.

Methods

Literature search for articles on the pathophysiology and treatment of ADPKD.

Results

Renal scanning with magnetic resonance imaging (MRI) represents the most sensitive tool for establishing both the diagnosis and prognosis for estimation of the risk of progression. Strict blood pressure control, preferably with angiotensin-converting enzyme (ACE) inhibitors, is the most crucial component of treatment. Selected patients with chronic kidney disease (CKD) stages I–III and a high probability of rapid progression to end-stage renal disease can benefit from treatment with tolvaptan, which has been shown to delay cyst growth and to reduce loss of the estimated glomerular filtration rate (eGFR).

Conclusion

In addition to non-specific treatment approaches, tolvaptan represents a treatment option for high risk ADPKD patients to inhibit progression of cyst growth and loss of eGFR.

     

Gastrointestinal symptoms,inflammation and hypoalbuminemia in chronic kidney disease patients: a cross-sectional study

Background

Few studies have focused on investigating hypoalbuminemia in patients during earlier stages of chronic kidney disease (CKD). In particular, little is known about the role of gastrointestinal (GI) symptoms. Our goal in this paper is to study how GI symptoms relate to serum albumin levels in CKD, especially in the context of and compared with inflammation.

Methods

We performed a cross-sectional study of 3599 patients with chronic kidney disease enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. All subjects were asked to complete the Modification of Diet in Renal Disease (MDRD) study patient symptom form. Our main predictor is GI symptom score. Serum level of C-reactive protein (CRP) was measured as well. Main outcome measures are serum albumin levels and prevalence of hypoalbuminemia.

Results

Of the participants assessed, mean serum albumin was 3.95?±?0.46 g/dL; 12.7 % had hypoalbuminemia. Patients with lower estimated glomerular filtration rate (eGFR) were likely to have more GI symptoms (apparent at an eGFR <45 ml/min/1.73 m²). Patients with worse GI symptoms had lower dietary protein intake. GI symptoms, like inflammation, were risk factors for lower serum albumin levels. However, adding GI symptom score or CRP into the multivariable regression analysis, did not attenuate the association between lower eGFR and lower albumin or hypoalbuminemia.

Conclusions

Increased prevalence of GI symptoms become apparent among CKD patients at relatively high eGFR levels (45 ml/min/1.73 m²), long before ESRD. Patients with more severe GI symptoms scores are more likely to have hypoalbuminemia. But our data do not support GI symptoms/decreased protein intake or inflammation as being the main determinants of serum albumin level in CKD patients.

     

Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study

Aims/hypothesis

Non-albuminuric renal impairment has become the prevailing diabetic kidney disease (DKD) phenotype in individuals with type 2 diabetes and an estimated GFR (eGFR) <60 ml min^?1 1.73 m^?2. In the present study, we compared the rate and determinants of all-cause death in individuals with this phenotype with those in individuals with albuminuric phenotypes.

Methods

This observational prospective cohort study enrolled 15,773 individuals with type 2 diabetes in 2006–2008. Based on baseline albuminuria and eGFR, individuals were classified as having: no DKD (Alb^?/eGFR^?), albuminuria alone (Alb⁺/eGFR^?), reduced eGFR alone (Alb^?/eGFR⁺), or both albuminuria and reduced eGFR (Alb⁺/eGFR⁺). Vital status on 31 October 2015 was retrieved for 15,656 individuals (99.26%).

Results

Mortality risk adjusted for confounders was lowest for Alb^?/eGFR^? (reference category) and highest for Alb⁺/eGFR⁺ (HR 2.08 [95% CI 1.88, 2.30]), with similar values for Alb⁺/eGFR^? (1.45 [1.33, 1.58]) and Alb^?/eGFR⁺ (1.58 [1.43, 1.75]). Similar results were obtained when individuals were stratified by sex, age (except in the lowest age category) and prior cardiovascular disease. In normoalbuminuric individuals with eGFR <45 ml min^?1 1.73 m^?2, especially with low albuminuria (10–29 mg/day), risk was higher than in microalbuminuric and similar to macroalbuminuric individuals with preserved eGFR. Using recursive partitioning and amalgamation analysis, prevalent cardiovascular disease and lower HDL-cholesterol were the most relevant correlates of mortality in all phenotypes. Higher albuminuria within the normoalbuminuric range was associated with death in non-albuminuric DKD, whereas the classic ‘microvascular signatures’, such as glycaemic exposure and retinopathy, were correlates of mortality only in individuals with albuminuric phenotypes.

Conclusions/interpretation

Non-albuminuric renal impairment is a strong predictor of mortality, thus supporting a major prognostic impact of renal dysfunction irrespective of albuminuria. Correlates of death partly differ from the albuminuric forms, indicating that non-albuminuric DKD is a distinct phenotype.

Trial registration:

ClinicalTrials.gov NCT00715481

     

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

BACKGROUND

Low molecular weight heparins (LMWHs) have been cautiously used in patients with chronic kidney disease (CKD) due to fear of accumulation. Dalteparin, however, has shown minimal tendency to accumulate in patients with CKD and may be safe to use in this patient population.

OBJECTIVE

We compared the incidence of clinically significant bleeding in patients with CKD receiving therapeutic doses of dalteparin to that of patients with CKD receiving therapeutic doses of UFH.

DESIGN

This was a retrospective cohort study.

SUBJECTS

Inpatients with CKD (GFR?<?60 ml/min) who were treated with therapeutic dalteparin or UFH were included in the study

MAIN MEASURES

Primary outcome was major bleeding within 10 days of anticoagulation, identified by ICD-9 code and confirmed by chart review. Demographic characteristics, laboratory values, comorbidities, prior bleeding history and inpatient medications were extracted for each admission from the electronic medical record. Logistic regression models were created to examine the association between choice of anticoagulant and bleeding rates, after adjustment for demographic and clinical characteristics.

KEY RESULTS

Dalteparin-treated patients were significantly less likely to experience a major bleed than patients treated with UFH (1.14 % vs. 3.49 %, p?<?0.001). The reduced likelihood of bleeding associated with dalteparin treatment remained significant after adjustment for patient characteristics (HR 0.39, 95 % CI: 0.21–0.70, p?<?0.0001). A stratified analysis for subgroups with GFR< 30 mL/min and with GFR between 30 and 60 mL/min showed that dalteparin was still associated with lower odds of bleeding compared to treatment with unfractionated heparin, but the difference was nonsignificant for GFR< 30 (HR 0.35, 95 % CI: 0.11–1.15), even after adjustment (OR 0.37, 95 % CI: 0.11–1.22).

CONCLUSION

In patients with CKD, treatment with therapeutic dose dalteparin was associated with lower rates of bleeding than treatment with unfractionated heparin. For patients with severe CKD (GFR< 30), dalteparin was shown to be at least as safe as unfractionated heparin.

     

Measurement of glomerular filtration rate in patients undergoing obesity surgery

Background

Most studies on obesity surgery have measured renal function using the estimated GFR. However, due to the reduction of muscle mass, and therefore creatinine that accompanies weight loss, such measures can falsely suggest an improvement in renal function. To balance the risks of surgery versus any potential benefits on renal function, we need to be able to determine renal function using valid and reliable methodologies. In this pilot study we aimed to measure renal function in patients with CKD undergoing obesity surgery using the gold standard ⁵¹Cr-EDTA GFR clearance methodology which is independent of measures of muscle mass.

Methods

Nine consecutive obese patients with CKD underwent obesity surgery. Their renal function was assessed using ⁵¹Cr-EDTA GFR, cystatin C and serum creatinine as well as using eGFR equations including MDRD CKD Epi, Cockcroft Gault and CKD Epi cystatin before and 12?months after surgery.

Results

Renal function using the ⁵¹Cr-EDTA measured GFR did not change significantly after surgery. Similar results were obtained when Cystatin C, CKD Epi cystatin, CKD Epi cystatin creatinine and adjusted Cockcroft Gault Creatinine clearance methods were used. In contrast there were either trends or significant improvements in renal function measured using the MDRD and CKD Epi equations.

Conclusions

In this pilot study using the gold standard ⁵¹Cr-EDTA method we found stabilisation in renal function after obesity surgery. Until further definitive data emerge it is critical to balance the risk and benefits of surgery, especially if renal function may not improve as often as previously suggested.

Trial registration

ClinicalTrials.gov NCT01507350. Registered June 2011.

     

SPRINT and the Kidney: What Have We Learned?

Purpose of Review

To review the impact of the Systolic Blood Pressure Interventional Trial (SPRINT) on renal function and chronic kidney disease.

Recent Findings

Hypertension is a risk factor for cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD). The benefits of intensive blood pressure lowering in the CKD population in previous studies are unclear. The SPRINT compared standard (<?140 mmHg) and intensive (<?120 mmHg) blood pressure management in nondiabetic patients with high risk of cardiovascular disease. In the subgroup of patients with CKD, the most important finding was that intensive blood pressure lowering is associated with lower risk of cardiovascular disease and mortality. Other than lower levels of albuminuria, there was no benefit on clinical kidney outcomes with the intensive treatment group. The risk of incident CKD and episodes of acute kidney injury was higher in patients in the intensive treatment group, though most patients with acute kidney injury recovered kidney function.

Summary

While the benefit of intensive blood pressure lowering on cardiovascular events and mortality with intensive blood pressure lowering is clear in patients with CKD, longer term follow-up may be needed to fully understand the effect on kidney function.

     

Comparison of automated and retrospectively calculated estimated glomerular filtration rate in electronic health record data

Background

Estimated glomerular filtration rate (eGFR) is the clinical standard for assessing kidney function and staging chronic kidney disease. Automated reporting of eGFR using the Modification of Diet in Renal Disease (MDRD) study equation was first implemented within the Department of Veterans Affairs (VA) in 2007 with staggered adoption across laboratories. When automated eGFR are not used or unavailable, values are retrospectively calculated using clinical and demographic data that are currently available in the electronic health record (EHR). Due to the dynamic nature of EHRs, current data may not always match past data. Whether and to what extent the practice of re-calculating eGFR on retrospective data differs from using the automated values is unknown.

Methods

We assessed clinical data for patients enrolled in VA who had their first automated eGFR lab in 2013.We extracted the eGFR value, the corresponding serum creatinine value, and patient race, gender, and date of birth from the EHR. The MDRD equation was applied to retrospectively calculate eGFR. Stage of chronic kidney disease (CKD) was defined using both eGFR values. We used Bland–Altman plots and percent agreement to assess the difference between the automated and calculated values. We developed an algorithm to select the most parsimonious parameter set to explain the difference in values and used chart review on a small subsample of patients to determine if one approach more accurately describes the patient at the time of eGFR measurement.

Results

We evaluated eGFR data pairs from 266,084 patients. Approximately 33.0% (n?=?86,747) of eGFR values differed between automated and retrospectively calculated methods. The majority of discordant pairs were classified as the same CKD stage (n?=?74,542, 85.93%). The Bland–Altman plot showed differences in the data pairs were centered near zero (mean difference: 0.8?mL/min/1.73m²) with 95% limits of agreement between ??6.4 and 8.0. A change in recorded age explained 95.6% (n?=?78,903) of discordant values and 85.02% (n?=?9371) of the discordant stages.

Conclusions

Values of retrospectively calculated eGFR can differ from automated values, but do not always result in a significant classification change. In very large datasets these small differences could become significant.

     

Diastolic function is a strong predictor of mortality in patients with chronic kidney disease

Background

Cardiovascular disease is a major cause of death in patients with stage 4–5 Chronic Kidney disease (CKD, eGFR <?30). There are only limited data on the risk factors predicting these complications in CKD patients. Our aim was to determine the role of clinical and echocardiographic parameters in predicting mortality and cardiovascular complications in CKD patients.

Methods

We conducted a prospective observational cohort study of 153 CKD patients between 2007 and 2009. All patients underwent echocardiography at baseline and were followed for a mean of 2.6 years using regular clinic visits and review of files and hospital presentations to record the incidence of cardiovascular events and death.

Results

Of 153 patients enrolled, 57 (37%) were on dialysis and 45 (78%) of these patients were on haemodialysis. An enlarged LV was present in 32% of patients and in 22% the LVEF was below 55%. LV mass index was increased in 75% of patients. Some degree of diastolic dysfunction was present in 85% of patients and 35% had grade 2 or higher diastolic dysfunction. During follow up 41 patients (27%) died, 15 (39%) from cardiovascular causes. Mortality was 24.0% in the non-dialysis patients versus 31.6% in patients on dialysis (p=ns). On multivariate analysis age >75 years, previous history of MI, diastolic dysfunction and detectable serum troponin T were significant independent predictor of mortality (P <?0.01).

Conclusion

Patients with stage 4–5 CKD had a mortality rate of 27% over a mean follow up of 2.6 years. Age >75 years, history of MI, diastolic dysfunction and troponin T were independent predictors of mortality.

     

Different Peptic Ulcer Bleeding Risk in Chronic Kidney Disease and End-Stage Renal Disease Patients Receiving Different Dialysis

Background

End stage renal disease (ESRD) patients receiving hemodialysis (HD) have a higher risk of peptic ulcer bleeding (PUB).

Aims

Whether ESRD patients receiving peritoneal dialysis (PD) also carries a higher risk of PUB has not been studied.

Methods

This was a cohort study using Taiwan’s National Health Insurance research database, whereby 11,408 patients, including 2,239 PD, 2,328 HD, 2,267 chronic kidney disease (CKD) and 4,574 controls with age–sex matching were recruited. The log-rank test was used to analyze differences in accumulated PUB-free survival rates between groups. Cox proportional hazard regression was performed to evaluate independent risk factors for PUB in all the enrollees.

Results

During the 7-year follow-up, PD and CKD patients had a significantly higher rate of PUB than matched controls. The risk of PUB between PD and CKD was not significantly different. Moreover, patients receiving HD carried a higher risk of PUB than those receiving PD, with CKD and controls (p all <0.05, by log-rank test). Cox proportional hazard regression analysis showed that CKD (HR 3.99, 95 % CI 2.24–7.13), PD (HR 3.71, 95 % CI 2.00–6.87) and HD (HR 11.96, 95 % CI 7.04–20.31) were independently associated with an increased risk of PUB. Being elderly, male, having hypertension, diabetes, cirrhosis, and nonsteroidal anti-inflammatory drugs and steroid use were other independent risk factors of PUB in all enrollees.

Conclusions

Patients with CKD and ESRD receiving PD or HD carried a higher risk for PUB. They should be screened for risk factors for PUB and receive some protective measures to prevent PUB.

     

Renal Effects of Incretin-Based Diabetes Therapies: Pre-clinical Predictions and Clinical Trial Outcomes

Purpose of Review

The purpose of this review is to correlate predictions based on pre-clinical data with outcomes from clinical trials that examine the effects of incretin-based diabetes treatments on the kidney. The incretin-based treatments include agonists of the glucagon-like peptide 1 receptor (GLP-1R) and inhibitors of the enzyme, dipeptidyl peptidase-4 (DPP-4). In addition, what is known about the incretin-based therapies will be compared to what is known about the renal effects of SGLT2 inhibitors.

Recent Findings

Large-scale clinical trials have shown that SGLT2 inhibitors reduce albuminuria and preserve estimated glomerular filtration rate (eGFR) in patients with diabetic nephropathy. A concise and plausible hemodynamic mechanism is supported by pre-clinical research on the physiology and pharmacology of SGLT2. Large-scale clinical trials have shown that incretin-based therapies mitigate albuminuria but have not shown beneficial effects on eGFR. Research on the incretin-based therapies has yielded a diverse array of direct effects throughout the body, which fuels speculation as to how these drugs might benefit the diabetic kidney and affect its function(s). But in vivo experiments have yet to confirm that the proposed mechanisms underlying emergent phenomena, such as proximal tubular fluid reabsorption, are the ones predicted by cell and molecular experiments.

Summary

There may be salutary effects of incretin-based treatments on the diabetic kidney, but the system is complex and not amenable to simple explanation or prior prediction. This contrasts with the renal effects of SGLT2 inhibitors, which can be explained concisely.

     

Urinary Neutrophil Gelatinase-Associated Lipocalin predicts the severity of contrast-induced acute kidney injury in chronic kidney disease patients undergoing elective coronary procedures

Background

Contrast-induced acute kidney injury (CI-AKI) particularly in high risk patients with chronic kidney disease (CKD), increases morbidity and mortality. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein excreted by the kidney during AKI. There are no urine (u) NGAL data as an early CI-AKI marker in CKD patients undergoing coronary procedures.

Methods

This prospective study enrolled 130 patients with estimated glomerular filtration rate (eGFR) <?60 ml/min/1.73 m² undergoing elective coronary procedures. Serial urine samples, obtained at baseline and 3, 6, 12, 18, and 24 h post contrast administration were analyzed by NGAL ELISA kit. AKI was defined as an increase in serum creatinine (SCr) of?≥?0.3 mg/dl or?≥?1.5 times baseline SCr within 48 h per 2012 KDIGO guidelines. Receiver operator characteristic curve analyses identified optimal uNGAL and delta of uNGAL values for diagnosing CI-AKI.

Results

The uNGAL was significantly and inverse correlated with eGFR (R =?0.25, P <?0.005). CI-AKI developed in 16/130 (12.31%) patients: 13 and 3 in CI-AKI stages I and II, respectively. uNGAL and delta of uNGAL were significantly higher in the CI-AKI group when compared with the No CI-AKI group (P <?0.05). The best uNGAL cut-off for optimal sensitivity 94%, specificity 78%, and area under the curve 0.84 for predicting CI-AKI was 117 ng/mL at 6 h, respectively. Corresponding values for predicting CI-AKI stage II were 100%, 87% and 0.9 when using an uNGAL of 264 ng/mL at 6 h.

Conclusions

Monitoring of uNGAL levels not only provide the early detecting CI-AKI but also predict the severity of CI-AKI in CKD patients undergoing elective coronary procedures.

     

Association between serum insulin-like growth factor I or IGF-binding protein 3 and estimated glomerular filtration rate: results of a population-based sample

Background

Insulin-like growth factor I (IGF-I), which is mostly carried in blood by IGF-binding protein 3 (IGFBP-3), was associated to the glomerular filtration rate and chronic kidney disease in a multiethnic study among US adults. The aim of the present study was to investigate whether serum IGF-I or IGFBP-3 are associated with estimated glomerular filtration rate (eGFR) in a population-based study of Caucasian adults.

Methods

Data from 4028 subjects (2048 women) aged 20 to 81 years from the Study of Health in Pomerania (SHIP) were analyzed. Total serum IGF-I and IGFBP-3 concentrations were determined by chemiluminescence immunoassays and categorized into sex- and age-specific quartiles.

Results

After adjusting for age, waist circumference and type 2 diabetes mellitus, analysis of variance (ANOVA) revealed inverse associations between serum IGF-I concentrations and eGFR in men as well as between serum IGFBP-3 concentrations and eGFR in men and women. Logistic regression analyses confirmed these findings and showed that high IGF-I or IGFBP-3 concentrations were associated with an increased risk of decreased eGFR (<60 mL/min/1.73 m²) in men or women. These relations became stronger when lower eGFR cut-offs were used for the analyses.

Conclusion

Our data revealed associations of increased serum IGF-I concentrations and decreased eGFR in men but not in women and an association of increased serum IGFBP-3 concentrations and decreased eGFR in both sexes.