Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33)

Aim/hypothesis

Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study.

Methods

Plasma copeptin, a surrogate for AVP, was measured in baseline samples from patients with type 2 diabetes treated in primary care and included in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort.

Results

Samples from 1,328 patients were available; 349 were analysed separately because they used renin–angiotensin–aldosterone system inhibition (RAASi), which influences albumin/creatinine ratio (ACR) and estimated (e)GFR. In the other 979 patients (46% men, age 68 years [58–75], ACR 1.8 mg/mmol [0.9–5.7], eGFR 67?±?14 ml min^?1 1.73 m^?2) baseline copeptin (5.3 pmol/l [3.2–9.5]) was significantly associated with log _e [ACR] and eGFR, even after adjustment for sex, age and risk factors for kidney function decline (standardised [std] β 0.13, p?<?0.001, std β ?0.20, p?<?0.001 respectively). Follow-up data were available for 756 patients (6.5 years [4.1–9.6]). Baseline copeptin was associated with increase in ACR (std β 0.09, p?=?0.02), but lost significance after adjustment (std β 0.07, p?=?0.08). Copeptin was associated with a decrease in eGFR after adjustment (std β ?0.09, p?=?0.03). The strength of the association of copeptin with change in eGFR was stronger than that of established risk factors for kidney function decline (e.g. BMI, HbA_1c). In patients who used RAASi there was a significant association between baseline copeptin and ACR and eGFR, but not with change in ACR and eGFR.

Conclusions/interpretation

In patients with diabetes not using RAASi a higher baseline copeptin concentration is significantly associated with higher baseline ACR and lower eGFR values and with a decline in eGFR during follow-up. This last association is independent of, and stronger than, most traditional risk factors for kidney function decline.     

Evidence for two distinct phenotypes of chronic kidney disease in individuals with type 1 diabetes mellitus

Aims/hypothesis

In a retrospective, observational, cross-sectional, single-centre study, we assessed the prevalence and correlates of different CKD phenotypes (with and without albuminuria) in a large cohort of patients of white ethnicity with type 1 diabetes.

Methods

From 2001 to 2009, 408 men and 369 women with type 1 diabetes (age 40.2 ± 11.7 years, diabetes duration 19.4 ± 12.2 years, HbA_1c 7.83 ± 1.17% [62.0 ± 12.9 mmol/mol]) were recruited consecutively. Albumin-to-creatinine ratio (ACR) and eGFR (Modification of Diet in Renal Disease) were obtained for all individuals, together with CKD stage. Diabetic retinopathy and peripheral polyneuropathy were detected in 41.5% and 8.1%, respectively, and cardiovascular disease (CVD) occurred in 8.5%. Adjudications of CKD phenotype were made by blinded investigators.

Results

Normo- (ACR <3.4), micro- (ACR 3.4–34) or macroalbuminuria (ACR ≥34 mg/mmol) were present in 91.6%, 6.4% and 1.9% of individuals, respectively. eGFR categories 1 (≥90 ml min^?1 [1.73 m]^?2), 2 (60–89 ml min^?1 [1.73 m]^?2) and 3 (<60 ml min^?1 [1.73 m]^?2) were present in 57.3%, 39.0% and 3.7%, respectively. The majority of participants had no CKD (89.4%), while stages 1–2 and ≥3 CKD were detected in 6.8% and 3.7%, respectively. The albuminuric (Alb⁺) and non-albuminuric (Alb^?) phenotypes were present in 12 (41.4%) and 17 (58.6%) individuals with stage ≥3 CKD, respectively. Individuals with an ACR <3.4 mg/mmol were subdivided into those with normal albuminuria (<1.1 mg/mmol; 77.2%) and mildly increased albuminuria (1.1–3.4 mg/mmol; 14.4%), and individuals with stage 2 CKD were subdivided into those with eGFR 75–89 ml min^?1 [1.73 m]^?2 and 60–74 ml min^?1 [1.73 m]^?2. ACR <3.4 mg/mmol (88.7%) and even <1.1 mg/mmol (70.4%) were common in individuals with eGFR 60–74 ml min^?1 [1.73 m]^?2. The prevalence of ACR <1.1 mg/mmol was lower but still significant (34.5%) in those with stage ≥3 CKD. In logistic regression analysis, stages 1–2 and ≥3 CKD were independently associated with age, HbA_1c, γ-glutamyltransferase, fibrinogen, hypertension, but not with sex, BMI, smoking, HDL-cholesterol or triacylglycerol. Inclusion of advanced retinopathy removed HbA_1c from the model. The CKD Alb⁺ phenotype correlated with diabetes duration, HbA_1c, HDL-cholesterol, fibrinogen and hypertension, while the CKD Alb^? phenotype was associated with age and hypertension, but not with diabetes duration, HbA_1c and fibrinogen.

Conclusions/interpretation

The Alb^? CKD phenotype is present in a significant proportion of individuals with type 1 diabetes supporting the hypothesis of two distinct pathways (Alb⁺ and Alb^?) of progression towards advanced kidney disease in type 1 diabetes. These are probably distinct pathways as suggested by different sets of covariates associated with the two CKD phenotypes.

     

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.

     

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.

     

Chronic kidney disease categories and renal–cardiovascular outcomes in type 2 diabetes without prevalent cardiovascular disease: a prospective cohort study (JDDM25)

Aims/hypothesis

In type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low- and high-risk diabetic patients.

Methods

This 4?year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine <176.8?μmol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; ml?min^?1 1.73?m^?2). Association of progression from ‘no CKD’ stage (ACR <3.5?mg/mmol and eGFR ≥90?ml?min^?1 1.73?m^?2) with risk for CVD onset was also evaluated.

Results

During follow-up (median 3.8?years), 89 CVD events occurred. Compared with patients with ‘no CKD’ as reference, those with ACR?≥?35.0?mg/mmol with co-existing eGFR 60–89?ml?min^?1 1.73?m^?2 or <60?ml?min^?1 1.73?m^?2 showed increased risk for CVD onset, whereas those with eGFR ≥90?ml?min^?1 1.73?m^?2 did not. Those with ACR <3.5?mg/mmol and eGFR <60?ml?min^?1 1.73?m^?2 did not show any increased risk. Among patients with ‘no CKD’ stage at baseline, those who progressed to ACR ≥3.5?mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR <90?ml?min^?1 1.73?m^?2 did not have increased risk.

Conclusions/interpretation

The risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD.     

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.

     

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

     

Serum 25-Hydroxyvitamin D Level and Kidney Function Decline in a Swiss General Adult Population

Background and objectives

Molecular evidence suggests that levels of vitamin D are associated with kidney function loss. Still, population-based studies are limited and few have considered the potential confounding effect of baseline kidney function. This study evaluated the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline, and incidence of CKD and albuminuria.

Design, setting, participants, & measurements

Baseline (2003–2006) and 5.5-year follow-up data from a Swiss adult general population were used to evaluate the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline (annual loss >3 ml/min per 1.73 m²), and incidence of CKD and albuminuria. Serum 25-hydroxyvitamin D was measured at baseline using liquid chromatography–tandem mass spectrometry. eGFR and albuminuria were collected at baseline and follow-up. Multivariate linear and logistic regression models were used considering potential confounding factors.

Results

Among the 4280 people included in the analysis, the mean±SD annual eGFR change was −0.57±1.78 ml/min per 1.73 m², and 287 (6.7%) participants presented rapid eGFR decline. Before adjustment for baseline eGFR, baseline 25-hydroxyvitamin D level was associated with both mean annual eGFR change and risk of rapid eGFR decline, independently of baseline albuminuria. Once adjusted for baseline eGFR, associations were no longer significant. For every 10 ng/ml higher baseline 25-hydroxyvitamin D, the adjusted mean annual eGFR change was −0.005 ml/min per 1.73 m² (95% confidence interval, −0.063 to 0.053; P=0.87) and the risk of rapid eGFR decline was null (odds ratio, 0.93; 95% confidence interval, 0.79 to 1.08; P=0.33). Baseline 25-hydroxyvitamin D level was not associated with incidence of CKD or albuminuria.

Conclusions

The association of 25-hydroxyvitamin D with eGFR decline is confounded by baseline eGFR. Sufficient 25-hydroxyvitamin D levels do not seem to protect from eGFR decline independently from baseline eGFR.     

Pulse wave reflection is associated with diabetes duration,albuminuria and cardiovascular disease in type 1 diabetes

Aims

We investigate associations between the pulse-wave-derived measures augmentation pressure (AP) and augmentation index, and diabetic complications in type 1 diabetes.

Methods

This cross-sectional study from 2009–2011 included 676 type 1 diabetes patients. SphygmoCor (Atcor Medical, Australia) measured AP and heart rate-adjusted augmentation index (AI75). Diabetic complications were micro- or macroalbuminuria [urinary albumin excretion rate (UAER) 30–299 or ≥300 mg/24-h], cardiovascular disease (CVD) (previous revascularization, myocardial infarction, peripheral arterial disease or stroke), autonomic dysfunction (heart rate variability <11 beats/min), or retinopathy (simple, proliferative or blindness). Adjustments included age, gender, diabetes duration, mean arterial pressure, heart rate, height, UAER, eGFR, HbA_1c, total cholesterol, total daily insulin dose, antihypertensive medication, and smoking.

Results

AP and AI75 measurements were available in 636 (94.1 %) patients and were 9.9 ± 7.6 mmHg and 16.9 ± 12.0, respectively. After adjustment, AP and AI75 were independently associated with diabetes duration and albuminuria (p ≤ 0.001). Furthermore, higher AP and AI75 were associated with previous CVD [adjusted odds ratios (95 % confidence interval) (per 1 SD increase) 1.9 (1.3–2.7) and 1.5 (1.0–2.2) (p ≤ 0.039)], but not with autonomic dysfunction or retinopathy (p ≥ 0.12).

Conclusions

In type 1 diabetes, augmentation pressure and heart rate-adjusted augmentation index were associated with diabetes duration, albuminuria, and CVD, independently of conventional risk factors. ClinicalTrials.gov:NCT01171248.     

In patients with type 1 diabetes simultaneous pancreas and kidney transplantation preserves long-term kidney graft ultrastructure and function better than transplantation of kidney alone

Aims/hypothesis

In patients with type 1 diabetes and end-stage renal disease (ESRD) we aimed to determine whether long-term normoglycaemia, as achieved by successful simultaneous pancreas and kidney (SPK) transplantation, would preserve kidney graft structure and function better than live donor kidney (LDK) transplantation alone.

Methods

Estimated GFR (eGFR) was calculated in SPK (n?=?25) and LDK (n?=?17) recipients in a stable phase 3 months after transplantation and annually during follow-up. Kidney graft biopsies were obtained at follow-up for measurement of glomerular volume (light microscopy), glomerular basement membrane (GBM) and podocyte foot process widths and mesangial volume fraction (electron microscopy).

Results

SPK and LDK recipients were similar in age and diabetes duration at engraftment. Donor age was higher in the LDK group. Median follow-up time was 10.1 years. Mean HbA_1c levels during follow-up were 5.5?±?0.4% (37?±?5 mmol/mol) and 8.3?±?1.5% (68?±?16 mmol/mol) in the SPK and LDK group, respectively (p?p?=?0.008) and increased mesangial volume fraction (median 0.23 [range 0.13–0.59] vs 0.16 [0.10–0.41]; p?=?0.007) at follow-up. Absolute eGFR change from baseline was ?11?±?21 and ?23?±?15 ml min^?1 1.73 m^?2 (p?=?0.060), whereas eGFR slope was ?1.1 (95% CI ?1.7, ?0.5) and ?2.6 (95% CI ?3.1, ?2.1)?ml min^?1 1.73 m^?2 per year in the SPK and LDK group, respectively (p?=?0.001).

Conclusions/interpretation

In patients with type 1 diabetes and long-term normoglycaemia after successful SPK transplantation, kidney graft ultrastructure and function were better preserved compared with LDK transplantation alone.     

Accuracy and limitations of equations for predicting the glomerular filtration rate during follow-up of patients with non-diabetic nephropathies

Background

Early detection of chronic kidney disease (CKD) is sub-optimal among the general population and among high risk patients. The prevalence and impact of major CKD risk factors, diabetes (DM) and hypertension (HTN), on CKD documentation among managed care populations have not been previously reported. We examined this issue in a Kaiser Permanente Georgia (KPG) CKD cohort.

Methods

KPG enrollees were included in the CKD cohort if they had eGFRs between 60 and 365 days apart that were <90 ml/min during 1999-2006. The current analysis is restricted to participants with eGFR 10-59 ml/min/1.73 m². CKD documentation was defined as a presenting diagnosis of CKD by a primary care physician or nephrologist using ICD-9 event codes. The association between CKD documentation and DM and HTN were assessed with multivariate logistic regression models.

Results

Of the 50,438 subjects within the overall KPG CKD cohort, 20% (N = 10,266) were eligible for inclusion in the current analysis. Overall, CKD diagnosis documentation was low; only 14.4% of subjects had an event-based CKD diagnosis at baseline. Gender and types 2 diabetes interacted on CKD documentation. The prevalence of CKD documentation increased with the presence of hypertension and/or type 2 diabetes, but type 2 diabetes had a lower effect on CKD documentation. In multivariate analysis, significant predictors of CKD documentation were eGFR, hypertension, type 2 diabetes, congestive heart failure, peripheral artery disease, statin use, age and gender. CKD documentation was lower among women than similarly affected men.

Conclusion

Among patients with an eGFR 10-59, documentation of CKD diagnosis by primary and subspecialty providers is low within a managed care patient cohort. Gender disparities in CKD documentation observed in the general population were also present among KPG CKD enrollees.     

Exercise as a Vital Sign: A Quasi-Experimental Analysis of a Health System Intervention to Collect Patient-Reported Exercise Levels

BACKGROUND

Lack of regular physical activity is highly prevalent in U.S. adults and significantly increases mortality risk.

OBJECTIVE

To examine the clinical impact of a newly implemented program (“Exercise as a Vital Sign” [EVS]) designed to systematically ascertain patient-reported exercise levels at the beginning of each outpatient visit.

DESIGN AND PARTICIPANTS

The EVS program was implemented in four of 11 medical centers between April 2010 and October 2011 within a single health delivery system (Kaiser Permanente Northern California). We used a quasi-experimental analysis approach to compare visit-level and patient-level outcomes among practices with and without the EVS program. Our longitudinal observational cohort included over 1.5 million visits by 696,267 adults to 1,196 primary care providers.

MAIN MEASURES

Exercise documentation in physician progress notes; lifestyle-related referrals (e.g. exercise programs, nutrition and weight loss consultation); patient report of physician exercise counseling; weight change among overweight/obese patients; and HbA1c changes among patients with diabetes.

KEY RESULTS

EVS implementation was associated with greater exercise-related progress note documentation (26.2 % vs 23.7 % of visits, aOR 1.12 [95 % CI: 1.11–1.13], p?<?0.001) and referrals (2.1 % vs 1.7 %; aOR 1.14 [1.11–1.18], p?<?0.001) compared to visits without EVS. Surveyed patients (n?=?6,880) were more likely to report physician exercise counseling (88 % vs. 76 %, p?<?0.001). Overweight patients (BMI 25–29 kg/m², n?=?230,326) had greater relative weight loss (0.20 [0.12 – 0.28] lbs, p?<?0.001) and patients with diabetes and baseline HbA1c?>?7.0 % (n?=?30,487) had greater relative HbA1c decline (0.1 % [0.07 %–0.13 %], p?<?0.001) in EVS practices compared to non-EVS practices.

CONCLUSIONS

Systematically collecting exercise information during outpatient visits is associated with small but significant changes in exercise-related clinical processes and outcomes, and represents a valuable first step towards addressing the problem of inadequate physical activity.     

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.

     

Prevalence of chronic kidney disease and associated factors among the Chinese population in Taian,China

Background

This study was designed to assess the prevalence of chronic kidney disease (CKD) and associated risk factors among the Chinese population in Taian, China.

Methods

A primary care-based cross-sectional study was conducted in Taian, China, from September to December 2012. Participants selected by a multi-stage stratified cluster sampling procedure were interviewed and tested for hematuria, albuminuria, estimated glomerular filtration rate (eGFR) and other clinical indices. Factors associated with CKD were analyzed by univariate and multivariate logistic regression analysis.

Results

A total of 14,399 subjects were enrolled in this study. The rates of hematuria, albuminuria and reduced eGFR were 4.20%, 5.25% and 1.89%, respectively. Approximately 9.49% (95% CI: 8.93%–10.85%) of the participants had at least one indicator of CKD, with an awareness of 1.4%. Univariate analyses showed that greater age, body mass index, and systolic and diastolic blood pressure; higher levels of serum creatinine, uric acid, fasting blood glucose, triglycerides, total cholesterol and low-density lipoprotein cholesterol; and lower eGFR were associated with CKD (p?<?0.05 each). Multivariate analysis showed that age, female gender, educational level, smoking habits, systolic blood pressure, and history of diabetes mellitus, hyperlipidemia, hypercholesterolemia and hyperuricemia were independent risk factors for CKD.

Conclusions

The prevalence of CKD in the primary care population of Taian, China, is high, although awareness is quite low. Health education and policies to prevent CKD are urgently needed among this population.

     

Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Aims/hypothesis

We investigated effects of renal function and albuminuria on cardiovascular outcomes in 9,795 low-risk patients with diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

Methods

Baseline and year 2 renal status were examined in relation to clinical and biochemical characteristics. Outcomes included total cardiovascular disease (CVD), cardiac and non-cardiac death over 5?years.

Results

Lower estimated GFR (eGFR) vs eGFR ??90?ml?min^?1 1.73?m^?2 was a risk factor for total CVD events: (HR [95% CI] 1.14 [1.01?C1.29] for eGFR 60?C89?ml?min^?1 1.73?m^?2; 1.59 [1.28?C1.98] for eGFR 30?C59?ml?min^?1 1.73?m^?2; p?<?0.001; adjusted for other characteristics). Albuminuria increased CVD risk, with microalbuminuria and macroalbuminuria increasing total CVD (HR 1.25 [1.01?C1.54] and 1.19 [0.76?C1.85], respectively; p?=?0.001 for trend) when eGFR ??90?ml?min^?1 1.73?m^?2. CVD risk was further modified by renal status changes over the first 2?years. In multivariable analysis, 77% of the effect of eGFR and 81% of the effect of albumin:creatinine ratio were accounted for by other variables, principally low HDL-cholesterol and elevated blood pressure.

Conclusions/interpretation

Reduced eGFR and albuminuria are independent risk factors for cardiovascular events and mortality rates in a low-risk population of mainly European ancestry. While their independent contributions to CVD risk appear small when other risk factors are considered, they remain excellent surrogate markers in clinical practice because they capture risk related to a number of other characteristics. Therefore, both should be considered when assessing prognosis and treatment strategies in patients with diabetes, and both should be included in risk models.     

Prevalence of systolic and diastolic dysfunction in patients with type 1 diabetes without known heart disease: the Thousand & 1 Study

Aims/hypothesis

Heart failure is one of the leading causes of mortality in type 1 diabetes. Early identification is vitally important. We sought to determine the prevalence and clinical characteristics associated with subclinical impaired systolic and diastolic function in type 1 diabetes patients without known heart disease.

Methods

In this cross-sectional examination of 1,093 type 1 diabetes patients without known heart disease, randomly selected from the Steno Diabetes Center, complete clinical and echocardiographic examinations were performed and analysed in uni- and multivariable regression models.

Results

The mean (SD) age was 49.6 (15)?years, 53% of participants were men, and the mean duration of diabetes was 25.5 (15)?years. Overall, 15.5% (n?=?169) of participants had grossly abnormal systolic or diastolic function, including 1.7% with left ventricular ejection fraction (LVEF)?<?45% and 14.4% with evidence of long-standing diastolic dysfunction. In univariable models, clinical characteristics associated with abnormal myocardial function were: age (per 10 years), OR (95% CI) 2.1 (1.8, 2.4); diabetes duration (per 10 years), 1.7 (1.4, 1.9); systolic BP?≥?140 mmHg, 2.7 (1.9, 3.8); diastolic BP?≥?90 mmHg, 1.8 (1.0, 3.1); estimated (e)GFR?<?60 ml min^?1 1.73 m^?2, 3.8 (2.5, 5.9); microalbuminuria, 2.0 (1.3, 3.0); macroalbuminuria, 5.9 (3.8, 9.3); proliferative retinopathy, 3.6 (2.3, 5.8); blindness, 10.1 (3.2, 31.6); and peripheral neuropathy, 3.8 (2.7, 5.3). In multivariable models only age (2.1 [1.7, 2.5]), female sex, (1.9 [1.2, 2.8]) and macroalbuminuria (5.2 [2.9, 10.3]) remained significantly associated with subclinical grossly abnormal myocardial function.

Conclusions/interpretation

Subclinical myocardial dysfunction is a common finding in type 1 diabetes patients without known heart disease. Type 1 diabetes patients with albuminuria are at greatly increased risk of having subclinical abnormal myocardial function compared with patients without albuminuria. Echocardiography may be particularly warranted in patients with albuminuria.     

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.

     

Mortality and morbidity in relation to changes in albuminuria,glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies

Aims/hypothesis

Urinary albumin excretion is a strong predictor of cardiovascular disease. It is uncertain whether improvement from microalbuminuria or deterioration from normoalbuminuria over time in patients with differing changes in glucose and BP change their cardiovascular risk.

Methods

Data on mortality, cardiovascular and renal outcomes were analysed in 22,984 patients from two large parallel randomised clinical trials followed for 56 months. A central laboratory analysed first morning spot urine samples at baseline and after 24 months, and events were recorded over the subsequent 32 months. Patients were stratified by changes in albuminuria, glucose status and mean systolic BP over 2 years.

Results

There was a strong association between albuminuria status and all-cause and cardiovascular mortality and combined cardiovascular and renal endpoints (all p?p?=?0.0004).

Conclusions/interpretation

Patients who showed improvement to normoalbuminuria over 2 years were at lower risk of all-cause and cardiovascular mortality and of cardiovascular and renal events than those who deteriorated to microalbuminuria over time. Albuminuria over time was significantly better than glucose status and BP control in predicting mortality and both cardiovascular and renal outcomes in patients at a high cardiovascular risk.     

Roux-en-Y gastric bypass vs sleeve gastrectomy for obese patients with type 2 diabetes: a randomised trial

Aims/hypothesis

Bariatric surgery is gaining acceptance as a ‘metabolic surgical intervention’ for patients with type 2 diabetes. The optimal form of surgery and the mechanism of action of these procedures are much debated. We compared two bariatric procedures for obese patients with type 2 diabetes and evaluated their effects on HbA_1c and glucose tolerance.

Methods

We performed a parallel un-blinded randomised trial of Roux-en-Y gastric bypass (RYGB) vs sleeve gastrectomy (SG) in 41 obese patients with type 2 diabetes, who were bariatric surgery candidates attending the obesity clinic. HbA_1c, body composition and glucose tolerance were evaluated at baseline, and at 3 and 12 months.

Results

Of the 41 patients, 37 completed the follow-up (19 RYGB, 18 SG). Both groups had similar baseline anthropometric and biochemical measures, and showed comparable weight loss and fat:fat-free mass ratio changes at 12 months. A similar normalisation of HbA_1c levels was observed as early as 3 months post-surgery (6.37?±?0.71% vs 6.23?±?0.69% for RYGB vs SG respectively, p?<?0.001 in both groups for baseline vs follow-up).

Conclusions/interpretation

In this study, RYGB did not have a superior effect in comparison to SG with regard to HbA_1c levels or weight loss during 12 months of follow-up.

Trial registration

ClinicalTrials.gov NCT00667706

Funding

This work was supported by grant no. 3-000-8480 from the Israel Ministry of Health Chief Scientist, the Stephen Morse Diabetes Research Foundation and by Johnson & Johnson.     

Renal impairment and coronary collaterals in patients with acute coronary syndrome

Objective

We aimed to elucidate the relationship between mild-to-moderate renal impairment and the development of coronary collateral vessels (CCV) in patients with acute coronary syndrome (ACS).

Methods

We enrolled 461 patients with ACS who underwent coronary angiography for the first time. The development of CCV was assessed with the Rentrop score. Kidney function was classified according to the estimated glomerular filtration rate (eGFR). The Gensini score was used to show the extent of atherosclerosis.

Results

The mean eGFR value was 89.9?±?24.3 U/l for patients with no development of collaterals and 82.7?±?20.5 for patients who had CCV. The mean age was 59?±?11 years and 349 patients (75.7?%) were male. Rentrop classifications 1-2-3 (presence of CCV) were determined in 222 (48.1?%) patients. The presence of CCV was significantly associated with low levels of eGFR (p?=?0.001), increased serum creatinine levels (p?=?0.034), high levels of serum albumin (0.036), and the Gensini score (p?<?0.001). Multivariate analysis showed that the Gensini score was an independent predictor of the presence of CCV (OR?=?1.090, 95?% CI: 1.032–1.151, p?=?0.002).

Conclusion

We suggest that the association between mild-to-moderate renal impairment and the presence of CCV may be explained by increased myocardial ischemia and severe CAD.