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.

     

The Landscape of Diabetic Kidney Disease in the United States

Purpose of Review

The purposes of this review are to identify population characteristics of important risk factors for the development and progression of diabetic kidney disease (DKD) in the United States and to discuss barriers and opportunities to improve awareness, management, and outcomes in patients with DKD.

Recent Findings

The major risk factors for the development and progression of DKD include hyperglycemia, hypertension, and albuminuria. DKD disproportionately affects minorities and individuals with low educational and socioeconomic status. Barriers to effective management of DKD include the following: (a) limited patient and healthcare provider awareness of DKD, (b) lack of timely referrals of patients to a nephrologist, (c) low patient healthcare literacy, and (d) insufficient access to healthcare and health insurance.

Summary

Increased patient and physician awareness of DKD has been shown to enhance patient outcomes. Multifactorial and multidisciplinary interventions targeting multiple risk factors and patient/physician education may provide better outcomes in patients with DKD.

     

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).

     

Risk of cardiovascular disease,death, and renal progression in diabetes according to albuminuria and estimated glomerular filtration rate

AimWe aimed to examine risks of major cardiovascular events (MACEs), renal outcomes, and all-cause mortality in type 2 diabetes mellitus (T2DM) patients with different diabetic kidney disease (DKD) subtypes.MethodsA total of 36,509 participants with T2DM recruited from 20 community sites across mainland China were followed up during 2011-2016. DKD subtypes were categorized based on albuminuria (urinary albumin-to-creatinine ratio, UACR ≥ 30 mg/g) and reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m²) as Alb^?/eGFR^?, Alb⁺/eGFR^?, Alb^?/eGFR⁺, and Alb⁺/eGFR⁺. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of developing clinical outcomes in DKD subtypes.ResultsMore than half (53.5%) of participants with diabetes and reduced eGFR had normal UACR levels (Alb^?/eGFR⁺), termed as non-albuminuria DKD. These patients had a modest increase in the risks of MACEs (hazard ratio, HR 1.42 [95% CI 1.08;1.88]) and mortality (HR 1.42 [1.04;1.92]) compared with patients without DKD, whereas CKD progression was not significantly increased (HR 0.97 [0.60;1.57]). Participants with albuminuria (Alb⁺/eGFR^? or Alb⁺/eGFR⁺) had higher risks of clinical outcomes. Subgroup analysis revealed that the associations between non-albuminuria DKD and risks of MACEs and mortality were more evident in those aged <65 years.ConclusionNon-albuminuria DKD accounts for more than half of DKD cases with low eGFR in Chinese diabetes patients. Diabetes patients with albuminuria are at higher risks of developing clinical outcomes and warrant early intervention, as well as patients with non-albuminuria DKD with age < 65 years.     

Renal function after repeat catheter ablation for long-standing persistent atrial fibrillation

Background

Renal impairment and atrial fibrillation (AF) often coexist. Catheter ablation is an effective way to reduce the burden of AF and improve symptoms; however, little is known about the relationship between renal function and AF and its role in the progression of AF for patients undergoing repeat catheter ablation.

Methods

In all, 171 patients with long-standing persistent AF ablation were enrolled in the study. The patients were divided into two groups according to their delta estimated glomerular filtration rate (eGFR) values, which was defined as the eGFR before the repeat procedure minus the eGFR before the initial procedure. Patients with decreasing eGFR (delta eGFR <?0) were categorized as group I, while individuals with no change or increasing eGFR (delta eGFR≥?0) were categorized as group II. eGFR was estimated at baseline and at the 12-month and 24-month follow-up visits.

Results

After a mean follow-up of 31.4?±?13.2 months, group I had a significantly higher arrhythmia recurrence rate than group II (71.2 vs. 49.2?%, p?<?0.001). On multivariable analyses, eGFR changes after the repeat procedure were associated with arrhythmia recurrence, hypertrophic cardiomyopathy, and CHA₂DS₂-VASc score. Patients with arrhythmia recurrence and those with a CHA₂DS₂-VASc score of ≥?3 were more likely to show an eGFR decline at follow-up.

Conclusion

Patients with long-standing persistent AF, with a failed initial ablation procedure and undergoing a repeat ablation procedure, appear to have a higher risk of arrhythmia recurrence. During the follow-up period, patients without arrhythmia recurrence and those with a CHA₂DS₂-VASc score of <?3 show improved renal function.

     

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.

     

Renal dysfunction,restrictive left ventricular filling pattern and mortality risk in patients admitted with heart failure: a 7-year follow-up study

Background

Renal dysfunction is associated with a variety of cardiac alterations including left ventricular (LV) hypertrophy, LV dilation, and reduction in systolic and diastolic function. It is common and associated with an increased mortality risk in heart failure (HF) patients. This study was designed to evaluate whether severe diastolic dysfunction contribute to the increased mortality risk observed in HF patients with renal dysfunction.

Methods

Using Cox Proportional Hazard Models on data (N?=?669) from the EchoCardiography and Heart Outcome Study (ECHOS) study we evaluated whether estimated glomerular filtration rate (eGFR) was associated with mortality risk before and after adjustment for severe diastolic dysfunction. Severe diastolic dysfunction was defined by a restrictive left ventricular filling pattern (RF) (=deceleration time?<?140 ms) by Doppler echocardiography.

Results

Median eGFR was 58 ml/min/1.73 m², left ventricular ejection fraction was 33% and RF was observed in 48%. During the 7 year follow up period 432 patients died. Multivariable adjusted eGFR was associated with similar mortality risk before (Hazard Ratio(HR)_{eGFR 10 ml increase}: 0.94 (95% CI: 0.89-0.99, P?=?0.024) and after (HR_{eGFR 10 ml increase}: 0.93 (0.89-0.99), P?=?0.012) adjustment for RF (HR: 1.57 (1.28-1.93), P?<?0.001).

Conclusions

In patients admitted with HF RF does not contribute to the increased mortality risk observed in patients with a decreased eGFR. Factors other than severe diastolic dysfunction may explain the association between renal function and mortality risk in HF patients.

     

Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in <Emphasis Type="Italic">ACE</Emphasis> and <Emphasis Type="Italic">TP53</Emphasis>

Background

Aboriginal Australians are at high risk of cardiovascular, metabolic and renal diseases, resulting in a marked reduction in life expectancy when compared to the rest of the Australian population. This is partly due to recognized environmental and lifestyle risk factors, but a contribution of genetic susceptibility is also likely.

Methods

Using results from a comprehensive survey of one community (N?=?1350 examined individuals), we have tested for familial aggregation of plasma glucose, arterial blood pressure, albuminuria (measured as urinary albumin to creatinine ratio, UACR) and estimated glomerular filtration rate (eGFR), and quantified the contribution of variation at four candidate genes (ACE; TP53; ENOS3; MTHFR).

Results

In the subsample of 357 individuals with complete genotype and phenotype data we showed that both UACR (h²?=?64%) and blood pressure (sBP h²?=?29%, dBP, h²?=?11%) were significantly heritable. The ACE insertion-deletion (P?=?0.0009) and TP53 codon72 polymorphisms (P?=?0.003) together contributed approximately 15% of the total heritability of UACR, with an effect of ACE genotype on BP also clearly evident.

Conclusions

While the effects of the ACE insertion-deletion on risk of renal disease (especially in the setting of diabetes) are well recognized, this is only the second study to implicate p53 genotype as a risk factor for albuminuria - the other being an earlier study we performed in a different Aboriginal community (McDonald et al., J Am Soc Nephrol 13: 677-83, 2002). We conclude that there are significant genetic contributions to the high prevalence of chronic diseases observed in this population.

     

Renal Hyperfiltration in Adolescents with Type 2 Diabetes: Physiology,Sex Differences,and Implications for Diabetic Kidney Disease

Purpose of Review

Compared to adult-onset type 2 diabetes (T2D), youth with T2D have a more aggressive phenotype with greater insulin resistance (IR), more rapid β cell decline, and higher prevalence of diabetic kidney disease (DKD).

Recent Findings

Hyperfiltration is common in youth with T2D and predicts progressive DKD. Hyperfiltration is a consequence of early changes in intrarenal hemodynamic function, including increased renal plasma flow (RPF) and glomerular pressure. Girls with T2D are disproportionally affected by DKD, with a 3-fold greater risk of developing hyperfiltration over 5 years compared to boys. Despite the high prevalence and gravity of DKD in youth-onset T2D, widely effective therapeutic options are lacking.

Summary

In this review, we focus on pathophysiology underlying early DKD in T2D and sex differences and summarize promising novel medical therapies and bariatric surgery.

     

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.

     

AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models,independent of adiponectin

Aims/hypothesis

In this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo.

Methods

Six-week-old male C57BL/6J wild-type and Adipoq ^?/? mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4–12. Diet-induced pathophysiology was examined in mice after 11 weeks by IPGTT and after 12 weeks by flow cytometry and western blotting. Human adipose tissue biopsies from obese (BMI 35–50 kg/m²) individuals were incubated with vehicle or AICAR (1 mmol/l) for 6 h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry.

Results

AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8⁺ T cells. AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p?<?0.05), urinary H₂O₂ (p?<?0.05) and renal superoxide levels (p?<?0.01) in both wild-type and Adipoq ^?/? mice. AICAR-mediated protection occurred independently of adiponectin, as similar protection was observed in wild-type and Adipoq ^?/? mice. In addition, AICAR promoted an M1-to-M2 macrophage phenotype switch and reduced TNF-α production in tissue explants from obese human patients.

Conclusions/interpretation

AICAR may promote metabolic health and protect against obesity-induced systemic diseases in an adiponectin-independent manner. Furthermore, AICAR reduced inflammation in human adipose tissue explants, suggesting by proof-of-principle that the drug may reduce obesity-induced complications in humans.

Trial registration:

ClinicalTrials.gov NCT02322073

     

Vasopressin-related copeptin is a novel predictor of early endothelial dysfunction in patients with adult polycystic kidney disease

Background

In this study, we examined the relative usefulness of serum copeptin levels as a surrogate marker of vasopressin (AVP) in adult polycystic kidney disease (ADPKD) by correlating it with baseline and longitudinal changes in markers of both renal function and common CVD manifestations (hypertensive vascular disease, atherosclerosis and endothelial dysfunction) that accompany the progression of this disease.

Methods

We studied a cohort of young and otherwise healthy ADPKD patients (n?=?235) and measured cardiovascular function using flow-mediation dilatation (FMD), carotid intima media thickness (cIMT) and pulse wave velocity (PWV), as well as serum copeptin (commercial ELISA, a stable marker of AVP activity). The same analyses were carried out at baseline and after 3 years of follow-up.

Results

At baseline, median eGFR was 69 mL/min./1.73 m², mean FMD 6.9?±?0.9%, cIMT 0.7?±?0.1 mm, and PWV 8.1?±?1.2 m/s. At follow-up, equivalent values were 65 (44–75) mL/min./1.73 m², 5.8?±?0.9%, 0.8?±?0.1 mm. and 8.2?±?1.3 m/s. with all changes statistically significant. Plasma copeptin also rose from 0.62?±?0.12 to 0.94?±?0.19 ng/mL and this change correlated with ΔeGFR (-0.33, p?<?0.001), ΔFMD (0.599, p?<?0.001), ΔcIMT (0.562, p?<?0.001) and ΔPWV (0.27, p?<?0.001) also after linear regression modeling to correct for confounders. Finally, ROC analysis was done for a high baseline copeptin with ΔeGFR [cut-off:≤59], ΔFMD [cut-off: ≤7.08], ΔcIMT [cut-off:>0.76], and ΔPWV [cut-off:≤7.80].

Conclusions

Vascular dysfunction as reflected by FMD and cIMT, but not PWV or an altered cardiac geometry, precede most other signs of disease in ADPKD but is predicted by elevated levels of the circulating AVP-marker copeptin.

     

Glomerular tip adhesions predict the progression of IgA nephropathy

Background

Focal segmental glomerulosclerosis-like lesions have been proposed to be predictive factors for IgA nephropathy. This single center, retrospective cohort study was designed to clarify which clinical and pathological factors are predictive of decreased estimated glomerular filtration rate (eGFR) at 5 and 10 years in IgA nephropathy patients.

Methods

Of the 229 patients with IgA nephropathy who were admitted to Aichi Medical University Hospital between 1986 and 2010, 57 were included in this study during the 5 to 10 years after renal biopsy. Clinical, laboratory, and pathological parameters were analyzed by multiple linear regression analysis with backward elimination to determine independent risk factors. After identifying such factors, we compared patients with and without each factor using the Student’s t test, Wilcoxon test, or Mann–Whitney U test.

Results

Four variables were identified as predictive factors for progression of IgA nephropathy: initial eGFR (p?=?0.0002), glomerular tip adhesion (p?=?0.004), global sclerosis (p?=?0.019), and diastolic blood pressure (p?=?0.024). The annual decrease in eGFR of patients with (n?=?9) or without glomerular tip adhesions (n?=?48) was 4.13?±?3.58 and 1.49?±?2.89 ml/min/1.73 m2, respectively (p?=?0.015). Serum total cholesterol levels were 231?±?45 mg/dl and 196?±?42 mg/dl, respectively (two-sided p?=?0.064; one-sided p?=?0.032).

Conclusions

The presence of glomerular tip adhesions predicts the progression of IgA nephropathy. High levels of serum total cholesterol may affect glomerular tip adhesions.

     

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.

     

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.

     

Albuminuria and its associated biomedical factors among indigenous adults in Far North Queensland: a 7-year follow up study

Background

To document albuminuria prevalence and its associated factors in Aboriginal and Torres Strait Islander (TSI) adults with high renal and metabolic risks from 19 rural and remote north Queensland communities.

Methods

One thousand nine hundred seventy-one indigenous adults were enrolled in 1998 and 566 completed follow up in 2007 in this population-based study. Measurements included weight, waist circumference (WC), blood pressure (BP), fasting glucose, lipids, gamma-glutamyltransferase (GGT), urinary albumin creatinine ratio (UACR), smoking, alcohol intake and physical activity (PA). Albuminuria was defined as an UACR?>?=2.5 g/mol in males and?>?=3.5 g/mol in females. The association between albuminuria and biomedical factors was assessed with generalised linear modelling.

Results

Baseline albuminuria prevalence was 19.7 % (95 % CI: 18.0–21.6 %). Follow up prevalence was 42.4 % (95 % CI: 38.4–46.5 %) among the 566 adults having the 2^nd UACR measurements. Follow-up albuminuria was associated with fasting glucose of 5.4 mmol/L (OR 2.5, 95 % CI 1.5–4.2), GGT tertiles in a dose-response manner (OR 2.0 for 2^nd and 3.7 for 3^rd tertile, p for trend <0.001), and abdominal overweight and obesity (OR 2.1, 95 % CI 1.1–3.9 and 5.4, 95 % CI: 2.2–13.5 respectively). Aboriginal people with diabetes were three times more likely of having albuminuria compared to TSI counterparts, while TSI smokers had twice the likelihood (95 % CI 1.2–3.2). At both baseline and follow up, albuminuria was more prevalent among older participants.

Conclusions

Indigenous Australians in north Queensland are at high risk of albuminuria. Overweight and obesity, glycaemia, increased GGT, and smoking were associated with albuminuria at baseline and/or follow up.

     

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.

     

Diabetic Kidney Disease: Is There a Role for Glycemic Variability?

Purpose of Review

Diabetes is the leading cause of kidney disease globally. Diabetic kidney disease (DKD) is a heterogeneous disorder manifested as albuminuria and/or decreasing GFR. Hyperglycemic burden is the major contributor to the development of DKD. In this article, we review the evidence for the contribution of glycemic variability and the pitfalls associated with use of hemoglobin A1c (A1C), the gold standard for assessment of glucose control, in the setting of DKD.

Recent Findings

Glycemic variability, characterized by swings in blood glucose levels, can result in generation of mitochondrial reactive oxygen species, a putative inciting factor for hyperglycemia-induced alterations in intracellular metabolic pathways. While there is indirect evidence supporting the role of glycemic variability in the pathogenesis of DKD, definitive data are lacking. A1C has many limitations and is a particularly suboptimal measure in patients with kidney disease, because its accuracy is compromised by variables affecting RBC survival and other factors. Continuous glucose monitoring (CGM) technology has the potential to enable us to use glucose as a more important clinical tool, for a more definitive understanding of glucose variability and its role in DKD.

Summary

Glycemic variability may be a factor in the development of DKD, but definitive evidence is lacking. Currently, all available glycemic biomarkers, including A1C, have limitations and in the setting of DKD and should be used cautiously. Emerging data suggest that personal and professional CGM will play an important role in managing diabetes in patients with DKD, where risk of hypoglycemia is high.

     

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.