Albuminuria In People Research Articles

Cumulative Effects of Aldosterone Synthase and SGLT2 Inhibition on Albuminuria in People with CKD

Cumulative Effects of Aldosterone Synthase and SGLT2 Inhibition on Albuminuria in People with CKD

Urine Albumin-Creatinine Ratio Variability in People With Type 2 Diabetes: Clinical and Research Implications

Evidence has demonstrated that albuminuria is a key diagnostic and prognostic marker of diabetic chronic kidney disease, but the impact of its day-to-day variability has not been adequately considered. This study quantified within-individual variability of albuminuria in people with type 2 diabetes to inform clinical albuminuria monitoring. Descriptive cross-sectional analysis. People with type 2 diabetes (n=826, 67.1 [IQR, 60.3-72.4] years, 64.9% male) participating in the Progression of Diabetic Complications (PREDICT) cohort study. Four spot urine collections for measurement of urinary albumin-creatinine ratio (UACR) within 4 weeks. Variability of UACR. We characterized within-individual variability (coefficient of variation [CV], 95% limits of random variation, intraclass correlation coefficient), developed a calculator displaying probabilities that any observed difference between a pair of UACR values truly exceeded a 30% difference, and estimated the ranges of diagnostic uncertainty to inform a need for additional UACR collections to exclude or confirm albuminuria. Multiple linear regression examined factors influencing UACR variability. We observed high within-individual variability (CV 48.8%; 95% limits of random variation showed a repeated UACR to be as high/low as 3.78/0.26 times the first). If a single-collection UACR increased from 2 to 5mg/mmol, the probability that UACR actually increased by at least 30% was only 50%, rising to 97% when 2 collections were obtained at each time point. The ranges of diagnostic uncertainty were 2.0-4.0mg/mmol after an initial UACR test, narrowing to 2.4-3.2 and 2.7-2.9mg/mmol for the mean of 2 and 3 collections, respectively. Some factors correlated with higher (female sex; moderately increased albuminuria) or lower (reduced estimated glomerular filtration rate and sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment) within-individual UACR variability. Reliance on the mean of 4 UACR collections as the reference standard for albuminuria. UACR demonstrates a high degree of within-individual variability among individuals with type 2 diabetes. Multiple urine collections for UACR may improve capacity to monitor changes over time in clinical and research settings but may not be necessary for the diagnosis of albuminuria. Albuminuria (albumin in urine) is a diagnostic and prognostic marker of diabetic chronic kidney disease. However, albuminuria can vary within an individual from day to day. We compared 4 random spot urinary albumin-creatinine ratio (UACR) samples from 826 participants. We found that a second UACR collection may be as small as a fourth or as large as almost 4 times the first sample's UACR level. This high degree of variability presents a challenge to our ability to interpret changes in albuminuria. Multiple collections have been suggested as a solution. We have constructed tools that may aid clinicians in deciding how many urine collections are required to monitor and diagnose albuminuria. Multiple urine collections may be required for individual monitoring but not necessarily for diagnosis.

Predictors and determinants of albuminuria in people with prediabetes and diabetes based on smoking status: A cross-sectional study using the UK Biobank data.

SummaryBackgroundSmoking is attributed to both micro- and macrovascular complications at any stage of metabolic deregulation including prediabetes. Current global diabetes prevention programmes appear to be glucocentric, and do not fully acknowledge the ramifications of cardiorenal risk factors in smokers and ex-smokers. A more holistic approach is needed to prevent vascular complications in people with prediabetes and diabetes before and after quitting.MethodsA cross-sectional study was carried out on participants who agreed to take part in the UK Biobank dataset at the time of their first attendances between March 01, 2006, and December 31, 2010. Those who had their urinary albumin concentration (UAC) data available were included, and those who did not have this data, were excluded. A logistic regression model was fitted to explore the relationship between cardiorenal risk factors and albuminuria in people with prediabetes and diabetes, based on smoking status.FindingsA total of 502,490 participants were included in the UK Biobank dataset. Of them, 30.4% (n=152,896) had their UAC level recorded. Compared with non-smokers, the odds of albuminuria in smokers with prediabetes and diabetes were 1.21 (95% CI 1.05 – 1.39, p=0.009), and 1.26 (95% CI 1.10 – 1.44, p=0.001), respectively. The odds declined after quitting in both groups, but it was not statistically significant (p>0.05). Each unit increase in HbA1c was associated with equivalent increased odds of albuminuria in current and ex-smokers, OR 1.035 (95% CI 1.030 – 1.039, p<0.001), and 1.026 (95% CI 1.023 – 1.028, p <0.001), respectively. Compared to females, male ex-smokers were at 15% increased odds of albuminuria. In ex-smokers, each unit increase in waist circumference was associated with 1% increased risk of albuminuria. Compared with the least deprived quintiles, the odds of albuminuria in the most deprived quintiles, in current and ex-smokers were identical, OR 1.18 (95% CI 1.04–1.324, p=0.010), and 1.19 (95% CI 1.11 – 1.27, p<0.001), respectively.InterpretationMale smokers are at a higher risk of albuminuria after smoking cessation. Monitoring waist circumference in quitters may identify those who are at a higher risk of albuminuria. Combining smoking cessation intervention in smokers with prediabetes in the current diabetes prevention programmes may offset post-cessation weight gain and reduce the risk of albuminuria.FundingUniversity of Sheffield.

Making an impact on kidney disease in people with type 2 diabetes: the importance of screening for albuminuria.

Albuminuria is useful for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden. Identifying patients with CKD who are most likely to progress to ESKD permits timely implementation of appropriate interventions. The early stages of CKD are asymptomatic, which means identification of CKD relies on routine assessment of kidney damage and function. Both albuminuria and estimated glomerular filtration rate are measures of kidney function. This review discusses albuminuria as a marker of kidney damage and cardiorenal risk, highlights the importance of early screening and routine testing for albuminuria in people with T2D, and provides new insights on the optimum management of CKD in T2D using albuminuria as a target in a proposed algorithm. Elevated urine albumin can be used to detect CKD in people with T2D and monitor its progression; however, obstacles preventing early detection exist, including lack of awareness of CKD in the general population, poor adherence to clinical guidelines, and country-level variations in screening and treatment incentives. With albuminuria being used as an entry criterion and a surrogate endpoint for kidney failure in clinical trials, and with novel treatment interventions available to prevent CKD progression, there is an urgent need for early screening and diagnosis of kidney function decline in people with T2D or pre-diabetes.

407-P: Skin Autofluorescence Is Associated with Tubular Injury Represented by Urinary Excretion of Liver-Type Fatty Acid–Binding Protein in People with Diabetes

Background: Advanced glycation end product (AGE) accumulation is thought to be an independent predictor for cardiovascular disease in people with diabetes and renal failure. Since it has remained unclear whether AGE has a clinical impact on diabetic kidney disease (DKD) , the aim of this study was to determine the association between AGE accumulation, measured as skin autofluorescence (AF) , and the progression of DKD. Methods: Skin AF was measured by AGE reader® and spot urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP) , were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 300 Japanese people with diabetes (173 males and 127 females, mean age, 67.8 ± 10.7 years) . The relationships between skin AF and those urine biomarkers of DKD were statistically evaluated. Results: Simple regression analysis showed that skin AF was associated with uACR (p&amp;lt;0.05) , log-transformed uACR (p&amp;lt;0.01) and uL-FABPCR (p&amp;lt;0.001) . On the other hand, multivariate regression analysis including clinical confounding factors showed that skin AF independently contributed to the increment of uL-FABPCR (P &amp;lt;0.05) but not to that of uACR (P=0.399) or log-transformed uACR (P=0.315) . Conclusion: Skin AF was associated with urinary L-FABP but not with albuminuria in people with diabetes. The results suggest that skin AF can serve as a novel predictive factor for the development of diabetic tubular injury. Disclosure H.Yamagami: None. T.Yuasa: None. S.Yoshida: None. A.Kuroda: None. M.Matsuhisa: Research Support; Nissui , Sysmex Corp., Speaker's Bureau; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. I.Endo: None. K.Aihara: None. M.Abe: None. S.Yasui: None. M.Hosoki: None. T.Hori: None. T.Hara: None. Y.Mitsui: None. K.Kurahashi: None. S.Nakamura: None. T.Otoda: None.

Predictors and Determinants of Albuminuria in People with Prediabetes and Diabetes Based on Smoking Status: A Cross-Sectional Study Using the UK Biobank Data

Predictors and Determinants of Albuminuria in People with Prediabetes and Diabetes Based on Smoking Status: A Cross-Sectional Study Using the UK Biobank Data

Role of the adaptive immune system in diabetic kidney disease.

Diabetic kidney disease (DKD) is a highly prevalent complication of diabetes and the leading cause of end‐stage kidney disease. Inflammation is recognized as an important driver of progression of DKD. Activation of the immune response promotes a pro‐inflammatory milieu and subsequently renal fibrosis, and a progressive loss of renal function. Although the role of the innate immune system in diabetic renal disease has been well characterized, the potential contribution of the adaptive immune system remains poorly defined. Emerging evidence in experimental models of DKD indicates an increase in the number of T cells in the circulation and in the kidney cortex, that in turn triggers secretion of inflammatory mediators such as interferon‐γ and tumor necrosis factor‐α, and activation of cells in innate immune response. In human studies, the number of T cells residing in the interstitial region of the kidney correlates with the degree of albuminuria in people with type 2 diabetes. Here, we review the role of the adaptive immune system, and associated cytokines, in the development of DKD. Furthermore, the potential therapeutic benefits of targeting the adaptive immune system as a means of preventing the progression of DKD are discussed.

Kidney outcomes and all-cause mortality in people with type 2 diabetes exhibiting non-albuminuric kidney insufficiency.

It remains unclear whether people with diabetes exhibiting non-albuminuric kidney insufficiency have higher risk of kidney function decline and mortality compared with those exhibiting preserved kidney function without albuminuria. Furthermore, information regarding the incidence of albuminuria in people with this unique phenotype is sparse. Here, we aimed to elucidate the risk of the kidney outcomes and all-cause mortality in people with diabetes exhibiting non-albuminuric kidney insufficiency. In this retrospective cohort study, 8320 Japanese adults with type 2 diabetes were classified into four groups based on the presence of albuminuria and kidney insufficiency at baseline, defined as urinary albumin/creatinine ratio of equal to or above 30mg/g and eGFR of less than 60 ml min-1 1.73 m-2, respectively. The primary composite kidney endpoint was a 50% decrease in eGFR from baseline or the initiation of kidney replacement therapy. The annual percentage change in eGFR slope and progression of albuminuria category were evaluated as the secondary and tertiary kidney endpoints, respectively. All-cause death was also set as the endpoint. Compared with people exhibiting non-albuminuric preserved kidney function, those with non-albuminuric kidney insufficiency had the higher risk for the primary kidney endpoint (HR 4.1; 95% CI 2.5, 6.7; p < 0.001), steep percentage change in eGFR slope (-1.96%/year vs -1.36%/year, p < 0.001), incidence of albuminuria (HR 2.1; 1.7, 2.6; p < 0.001) and all-cause mortality (HR 1.5; 1.2, 2.0; p = 0.003). In the sensitivity analyses treating the incidence of albuminuria as a competing risk, people with non-albuminuric kidney insufficiency still had higher risk for the primary kidney endpoint and all-cause mortality than those with non-albuminuric preserved kidney function (subdistribution HR 2.8; 1.4, 5.6; p = 0.004; and 1.6; 1.1, 2.2; p = 0.014, respectively). People with type 2 diabetes exhibiting non-albuminuric kidney insufficiency had poorer kidney outcomes and life prognosis than those exhibiting non-albuminuric preserved kidney function.

Altered dietary salt intake for people with chronic kidney disease.

Evidence indicates that reducing dietary salt may reduce the incidence of heart disease and delay decline in kidney function in people with chronic kidney disease (CKD). This is an update of a review first published in 2015. To evaluate the benefits and harms of altering dietary salt for adults with CKD. We searched the Cochrane Kidney and Transplant Register of Studies up to 6 October 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials comparing two or more levels of salt intake in adults with any stage of CKD. Two authors independently assessed studies for eligibility, conducted risk of bias evaluation and evaluated confidence in the evidence using GRADE. Results were summarised using random effects models as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included 21 studies (1197 randomised participants), 12 in the earlier stages of CKD (779 randomised participants), seven in dialysis (363 randomised participants) and two in post-transplant (55 randomised participants). Selection bias was low in seven studies, high in one and unclear in 13. Performance and detection biases were low in four studies, high in two, and unclear in 15. Attrition and reporting biases were low in 10 studies, high in three and unclear in eight. Because duration of the included studies was too short (1 to 36 weeks) to test the effect of salt restriction on endpoints such as death, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were examined. Reducing salt by mean -73.51 mmol/day (95% CI -92.76 to -54.27), equivalent to 4.2 g or 1690 mg sodium/day, reduced systolic/diastolic blood pressure by -6.91/-3.91 mm Hg (95% CI -8.82 to -4.99/-4.80 to -3.02; 19 studies, 1405 participants; high certainty evidence). Albuminuria was reduced by 36% (95% CI 26 to 44) in six studies, five of which were carried out in people in the earlier stages of CKD (MD -0.44, 95% CI -0.58 to -0.30; 501 participants; high certainty evidence). The evidence is very uncertain about the effect of lower salt intake on weight, as the weight change observed (-1.32 kg, 95% CI -1.94 to -0.70; 12 studies, 759 participants) may have been due to fluid volume, lean tissue, or body fat. Lower salt intake may reduce extracellular fluid volume in the earlier stages of CKD (-0.87 L, 95% CI -1.17 to -0.58; 3 studies; 187 participants; low certainty evidence). The evidence is very uncertain about the effect of lower salt intake on reduction in antihypertensive dose (RR 2.45, 95% CI 0.98 to 6.08; 8 studies; 754 participants). Lower salt intake maylead to symptomatic hypotension (RR 6.70, 95% CI 2.40 to 18.69; 6 studies; 678 participants; moderate certainty evidence). Data were sparse for other types of adverse events. We found high certainty evidence that salt reduction reduced blood pressure in people with CKD, and albuminuria in people with earlier stage CKD in the short-term. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in CKD progression and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted.

1028-P: Inside CKD: Modeling the Clinical and Economic Impact of Routine Screening for Albuminuria in People with Type 2 Diabetes

Background: Early chronic kidney disease (CKD) diagnosis in patients with type 2 diabetes (T2D) followed by guideline-recommended interventions are key to slowing CKD progression, but adherence to screening recommendations is suboptimal. Inside CKD models the global clinical and economic burden of CKD using country-specific, patient-level microsimulation models. We model the effects of targeted implementation of urine albumin:creatinine ratio (UACR) measurement and intervention in patients with T2D.Methods: We used the Inside CKD microsimulation to model the impact of measuring UACR during routine primary care visits with subsequent intervention in patients with T2D aged ≥45 years, versus current practice. Virtual populations were constructed using published country-specific data on demographics, CKD, T2D, comorbidities and complications.Results: Preliminary data for three countries show that in 2020-2025, measurement of UACR in patients with T2D would prevent CKD progression to stages 3b-5 in 80 000 patients in the UK, 350 000 in the US and 70 000 in Canada (Figure). Associated cost savings would be £90M, $5B and C$1.7B. More countries will be analysed.Conclusion: Preliminary data show that routine UACR measurement with subsequent intervention could potentially reduce the global burden of CKD and healthcare costs in patients with T2D, and improve outcomes.View largeDownload slideView largeDownload slide DisclosureS. T. Nolan: Employee; Self; AstraZeneca, Employee; Spouse/Partner; Biomarin, Stock/Shareholder; Self; AstraZeneca, Stock/Shareholder; Spouse/Partner; Biomarin. J. Sanchez: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Halimi: None. E. Kanda: Speaker’s Bureau; Self; AstraZeneca K. K. G. Li: None. F. Mennini: None. J. Navarro-gonzalez: None. A. Power: Advisory Panel; Self; AstraZeneca, Bayer U. S., Napp Pharmaceuticals, Vifor Pharma Management Ltd., Consultant; Self; AstraZeneca, Speaker’s Bureau; Self; Alexion Pharmaceuticals, Inc., AstraZeneca, Napp Pharmaceuticals, Vifor Pharma Management Ltd. L. Retat: Employee; Self; HealthLumen. N. Tangri: Consultant; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., ClinPredict Inc, Eli Lilly and Company, Mesentech, Otsuka America Pharmaceutical, Inc., PulseData, Roche Pharma, Tricida, Inc., Research Support; Self; Janssen Pharmaceuticals, Inc. L. Webber: Employee; Self; HealthLumen. A. Sultan: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Wish: Advisory Panel; Self; Akebia Therapeutics, Inc., AstraZeneca, Rockwell Medical, Vifor Pharma Management Ltd., Speaker’s Bureau; Self; Akebia Therapeutics, Inc., AstraZeneca. M. Xu: Employee; Self; HealthLumen. J. Ärnlöv: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; Novartis AG. M. C. Batista: None. C. Cabrera: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Card-gowers: Employee; Self; HealthLumen. S. Chadban: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Novartis Pharmaceuticals Corporation. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. L. Denicola: Consultant; Self; AstraZeneca, Mundipharma International, Novo Nordisk.FundingAstraZeneca

Do SGLT-2 inhibitors reduce albuminuria in people with diabetes?

Indiana University School of Medicine, Arnett Family Medicine Residency, Lafayette, IN The authors declare no conflicts of interest.

525-P: Impact of Extracellular-to-Intracellular Fluid Volume Ratio on Albuminuria in People with Type 2 Diabetes: A Cross-Sectional and Retrospective Cohort Study

Body fluid volume imbalance is common in patients with kidney failure and is associated with all-cause mortality. We hypothesized that fluid volume imbalance occurs in diabetic patients without kidney failure and is associated with albuminuria. This study aimed to investigate the association between fluid volume imbalance and albuminuria in patients with type 2 diabetes without kidney failure. Body fluid imbalance was determined by measuring the extracellular water to intracellular water ratio (ECW/ICW) using bioelectrical impedance analysis. In the cross-sectional study of 432 participants, ECW/ICW increased with level of albuminuria (0.634 ± 0.002 in normo-, 0.645 ± 0.003 in micro- and 0.656 ± 0.004 in macroalbuminuria, all p &amp;lt;0.001 by Tukey’s HSD test). The log-transformed urinary ACR was associated with elevated ECW/ICW ratio (r =0.313, p &amp;lt;0.001) (Figure). In addition, there was an association between ECW/ICW ratio and logarithms urinary ACR after adjusting for covariates (β = 0.217, p &amp;lt;0.001) by multiple regression analysis. Moreover, in the retrospective studies of 368 participants, ECW/ICW was associated with change in the urinary ACR after adjusting for covariates (β = 0.171, p = 0.005) by multiple regression analysis. This reinforces the importance of monitoring fluid balance in diabetic patients. Disclosure H. Nakajima: None. Y. Hashimoto: None. T. Senmaru: None. H. Okada: None. M. Hamaguchi: None. M. Fukui: None.

Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

BackgroundCanagliflozin is a sodium–glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes.MethodsThe CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.ResultsThe mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal.ConclusionsIn two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754, respectively.)

Brain MRI Volume Findings in Diabetic Adults With Albuminuria: The ACCORD-MIND Study.

Albuminuria is associated with cognitive impairment in people with type 2 diabetes mellitus (T2DM). The brain volume correlates of albuminuria in people with T2DM have not been well investigated. We examined 502 individuals with T2DM (9-12 years duration; mean age ~62 years) who had a brain MRI at baseline and at 40 months. Baseline MRI findings were examined by the presence or absence of albuminuria (≥30mg/g creatinine). Changes in MRI findings were examined by whether albuminuria was persistent, intermittent, or absent during follow-up. At baseline, participants with albuminuria (28.7% of the cohort) had more abnormal white matter volume (AWMV) than participants without albuminuria on unadjusted analysis. This difference was attenuated with adjustment for systolic blood pressure, which was higher in participants with albuminuria than in those without albuminuria. During ~3.5 years of follow-up, participants with persistent albuminuria (15.8%) had a greater increase in new AWMV than participants without albuminuria (59.8%) or those with intermittent albuminuria on unadjusted analysis. This difference was attenuated with adjustment for age and systolic blood pressure. There were no significant differences in gray matter volume and total brain volume between participants with or without albuminuria at baseline or during follow-up. There was no significant effect modification of these findings by estimated glomerular filtration rate (eGFR) at baseline or change in eGFR during follow-up. In this diabetic cohort, baseline albuminuria and persistent albuminuria were not independently associated with any significant differences in brain volume measurements compared with participants without albuminuria.

Heart rate-corrected QT interval is a novel risk marker for the progression of albuminuria in people with Type2 diabetes.

A close association between heart rate-corrected QT interval (QTc) and albuminuria in people with Type2 diabetes has been reported in cross sectional studies. The aim of this study was to evaluate the relationship between QTc and change in urine albumin excretion (UAE) or progression of albuminuria in people with Type2 diabetes. We measured QTc in 251 consecutive people at baseline. We performed a 5-year follow-up cohort study to assess the relationship between QTc and change in UAE, defined as an increase of UAE/follow-up duration (year), or progression of albuminuria, defined as an increase in the category of diabetic nephropathy. During follow-up, 23 of 151 people with normoalbuminuria and 13 of 73 people with microalbuminuria at baseline had progression of albuminuria. Multiple regression analysis demonstrated that QTc was independently associated with change in UAE (β=0.176, P=0.0104). Logistic regression analyses showed that QTc was a risk marker for progression of albuminuria [odds ratio per 0.01-s increase in QTc 1.35, 95% confidence interval (CI) 1.11-1.66, P=0.0024] after adjusting for confounders. According to the receiver operator characteristic (ROC) analysis, the optimal cut-off point of QTc for progression of albuminuria was 0.418s [area under the ROC curve 0.75 (95% CI 0.66-0.82), sensitivity=0.86, specificity=0.56, P<0.0001]. Heart rate-corrected QT interval could be a novel risk marker for progression of albuminuria in people with Type2 diabetes.

Altered dietary salt intake for people with chronic kidney disease.

Salt intake shows great promise as a modifiable risk factor for reducing heart disease incidence and delaying kidney function decline in people with chronic kidney disease (CKD). However, a clear consensus of the benefits of reducing salt in people with CKD is lacking. This review evaluated the benefits and harms of altering dietary salt intake in people with CKD. We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We included randomised controlled trials (RCTs) that compared two or more levels of salt intake in people with any stage of CKD. Two authors independently assessed studies for eligibility and conducted risk of bias evaluation. Results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were calculated using the random-effects models. We included eight studies (24 reports, 258 participants). Because duration of the included studies was too short (1 to 26 weeks) to test the effect of salt restriction on endpoints such as mortality, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were applied. Three studies were parallel RCTs and five were cross-over studies. Selection bias was low in five studies and unclear in three. Performance and detection biases were low in two studies and unclear in six. Attrition and reporting biases were low in four studies and unclear in four. One study had the potential for high carryover effect; three had high risk of bias from baseline characteristics (change of medication or diet) and two studies were industry funded.There was a significant reduction in 24 hour sodium excretion associated with low salt interventions (range 52 to 141 mmol) (8 studies, 258 participants: MD -105.86 mmol/d, 95% CI -119.20 to -92.51; I(2) = 51%). Reducing salt intake significantly reduced systolic blood pressure (8 studies, 258 participants: MD -8.75 mm Hg, 95% CI -11.33 to -6.16; I(2) = 0%) and diastolic blood pressure (8 studies, 258 participants: MD -3.70 mm Hg, 95% CI -5.09 to -2.30; I(2) = 0%). One study reported restricting salt intake reduced the risk of oedema by 56%. Salt restriction significantly increased plasma renin activity (2 studies, 71 participants: MD 1.08 ng/mL/h, 95% CI 0.51 to 1.65; I(2) = 0%) and serum aldosterone (2 studies, 71 participants: 6.20 ng/dL (95% CI 3.82 to 8.58; I(2) = 0%). Antihypertensive medication dosage was significantly reduced with a low salt diet (2 studies, 52 participants): RR 5.48, 95% CI 1.27 to 23.66; I(2) = 0%). There was no significant difference in eGFR (2 studies, 68 participants: MD -1.14 mL/min/1.73 m(2), 95% CI -4.38 to 2.11; I(2) = 0%), creatinine clearance (3 studies, 85 participants): MD -4.60 mL/min, 95% CI -11.78 to 2.57; I(2) = 0%), serum creatinine (5 studies, 151 participants: MD 5.14 µmol/L, 95% CI -8.98 to 19.26; I(2) = 59%) or body weight (5 studies, 139 participants: MD -1.46 kg; 95% CI -4.55 to 1.64; I(2) = 0%). There was no significant change in total cholesterol in relation to salt restriction (3 studies, 105 participants: MD -0.23 mmol/L, 95% CI -0.57 to 0.10; I(2) = 0%) or symptomatic hypotension (2 studies, 72 participants: RR 6.60, 95% CI 0.77 to 56.55; I(2) = 0%). Salt restriction significantly reduced urinary protein excretion in all studies that reported proteinuria as an outcome, however data could not be meta-analysed. We found a critical evidence gap in long-term effects of salt restriction in people with CKD that meant we were unable to determine the direct effects of sodium restriction on primary endpoints such as mortality and progression to end-stage kidney disease (ESKD). We found that salt reduction in people with CKD reduced blood pressure considerably and consistently reduced proteinuria. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in ESKD incidence and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted, as is investigation into adherence to a low salt diet.

Effect of exercise on albuminuria in people with diabetes

Spot urine measurement of albumin is now the most commonly accepted approach to screening for proteinuria. Exertion prior to the collection may potentially influence the result of spot urine albumin estimation. We aim to evaluate the effect of exercise on albuminuria in subjects at various stages of diabetic nephropathy in comparison with healthy control volunteers. Thirty-five people with diabetes (19 with normoalbuminuria (NA), nine with microalbuminuria (MA) and seven with overt proteinuria (OP)) and nine control subjects were assessed. A 1 km treadmill walk was performed. Four spot urine specimens were collected: first morning void, immediately prior to exercise, and 1 h and 2 h after exercise. A random effects linear regression mixed model was used to assess the effect of exercise on albumin/creatinine ratio (uACR). Results are presented separately for male and female subjects with diabetes due to a significant exercise/gender interaction (P < 0.05). No significant effect of exercise on uACR was seen in control subjects. In NA males with diabetes no effect of exercise was seen, while in females uACR 1 h after exercise was significantly higher than the early morning sample (3.55 mg/mmol (96% confidence interval 0.27-6.83). Both female and male diabetes subjects with MA have increase in uACR 1 h after exercise (87.8, -24.3-199.4 and 6.7, 2.1-11.3). For both males and females with OP, uACR was significantly increased 1 h post exercise (67.5, 22-113 and 21.6, 8.4-34.8, respectively). In all groups uACR at 2 h after exercise was not significantly different to the early morning sample. Exercise increased uACR estimation in normoalbuminuric subjects with diabetes with a larger effect in females. Whether exercise unmasks early diabetic nephropathy in NA subjects requires further study.

Subclinical hypothyroidism is independently associated with albuminuria in people with type 2 diabetes

We examined a possible association between subclinical hypothyroidism and albuminuria in 159 people with type 2 diabetes. Patients with subclinical hypothyroidism had significantly higher levels of urinary albumin-to-creatinine ratio (UACR) than those with euthyroidism. Multivariate logistic regression analyses demonstrated that serum TSH level was an independent risk factor of albuminuria.

Cross-sectional Association Between Fish Consumption and Albuminuria: The European Prospective Investigation of Cancer–Norfolk Study

Studies have shown a potential beneficial role for fish and fish oil consumption in the management of diabetes and its complications. The aim of this study is to examine the association between fish consumption and albuminuria in individuals with and without diabetes. A cross-sectional analysis conducted in the European Prospective Investigation of Cancer-Norfolk population-based cohort study. 22,384 men and women from general practices in the city of Norwich and vicinity, of whom 517 had diabetes by self-report and 21,867 did not report diabetes. Fish consumption was measured in a validated semiquantitative food frequency questionnaire and categorized as less than 1, 1 to 2, and more than 2 portions/wk. Interaction between fish intake and diabetes status was hypothesized a priori. Microalbuminuria and macroalbuminuria were defined as urinary albumin-creatinine ratio of 2.5 or greater to 24.9 and 25 mg/mmol or greater, respectively. Log-transformed albumin-creatinine ratio was used as a continuous variable. Prevalences of microalbuminuria were 22.6% in participants with diabetes and 11.4% in participants without diabetes. Prevalences of macroalbuminuria were 8.3% and 0.6%, respectively. Fish consumption was associated with a lower risk of macroalbuminuria in participants with diabetes (odds ratio, 0.22, >2 versus <1 portion/wk; 95% confidence interval, 0.07 to 0.70; P for trend = 0.009) after adjustment for confounding. This association was not observed in participants with diabetes with microalbuminuria or in the nondiabetic population. There was a significant interaction between diabetes status and fish consumption of 1 to 2 portions/wk (P = 0.03) and more than 2 portions/wk (P = 0.007) for risk of macroalbuminuria. Cross-sectional nature of study. Self-report of fish intake and diabetes status. Greater fish intake was associated with a lower risk of macroalbuminuria in a self-defined diabetic population. These findings merit confirmation in prospective studies and intervention trials and suggest that fish intake may be beneficial for albuminuria in people with diabetes.

Value of Ambulatory Arterial Stiffness Index and 24-h Pulse Pressure to Predict Progression of Albuminuria in Elderly People With Diabetes Mellitus

Ambulatory 24-h pulse pressure predicts progression of albuminuria in people with diabetes mellitus. It is not known whether the ambulatory arterial stiffness index (AASI) may add to that prediction. We compared the multivariate-adjusted association of AASI and 24-h pulse pressure with progression of urine albumin excretion during follow-up in a multiethnic cohort of older people with type-2 diabetes mellitus. The baseline evaluation included office and 24-h ambulatory blood pressure (BP) measurements, and a spot urine measurement of albumin-to-creatinine ratio (ACR). The ACR measurements were repeated annually during 3 years. The AASI was >or=0.55 units in 47% of those exhibiting progression of albuminuria, and in 37% of those without progression (P = .004), whereas 24-h pulse pressure was >or=65 mm Hg in 50% and 38% of those with and without progression, respectively (P = .001). In repeated measures mixed linear model (n = 1043), after adjustment for several covariates including office pulse pressure, AASI in the fourth quartile was independently associated with higher follow-up ACR (P = .024). However, that association did not persist after adjusting for 24-h pulse pressure, which was an independent predictor (P < .001). Cox proportional hazards models examined progression of albuminuria in 957 participants without macroalbuminuria at baseline. The hazard ratio (95% CI) for AASI >or=0.55 units was 1.37 (1.02-1.83) after multivariable adjustment, including office pulse pressure. But AASI was not an independent predictor after adjustment for ambulatory pulse pressure, which was again an independent predictor (P = .033). Ambulatory 24-h pulse pressure outperformed AASI in predicting progression of albuminuria in elderly people with type 2 diabetes.