Albuminuria Stage Research Articles

Endotrophin is a risk marker of complications in CANagliflozin cardioVascular Assessment Study (CANVAS): a randomized controlled trial

BackgroundEnhanced de-novo collagen type VI (COL VI) formation has been associated with kidney and cardiovascular fibrosis. We hypothesized that endotrophin (ETP), a product specifically generated during collagen type VI formation, may be prognostic for heart failure (HF), cardiovascular death (CVD), kidney endpoints, and all-cause mortality in patients with type 2 diabetes.MethodsWe measured ETP in plasma (P-ETP) and urine (U-ETP) samples collected at baseline and follow-up (year 3) from the randomized controlled trial, CANagliflozin cardioVascular Assessment Study (CANVAS), by use of the PRO-C6 ELISA measuring COL VI formation and ETP. At baseline, plasma and urine samples were available for 3531 and 3423 patients, respectively. At year 3, plasma and urine samples were available for 2178 (61.7%) and 2070 (60.5%) patients, respectively Patients were followed for a median of 6.1 years, and endpoints included: incident HF, CVD, three kidney composite endpoints, and all-cause mortality. Backward selection was used to identify variables to be included in the analyses. Robustness of the association with outcome was assessed by bootstrap analyses.ResultsIn univariable analysis, P-ETP predicted all investigated outcomes (all p < 0.0001), remained independently associated with all outcomes after adjustment for conventional risk factors (all p < 0.004), and increased C-statistics of the models for the outcomes HF, CVD, HFCVD, all-cause mortality, and kidney composite 2 (ΔC ≥ 0.002). In bootstrap analysis, P-ETP was retained with a frequency ranging from 41.0 to 98.4% for all outcomes. Levels of U-ETP were associated with outcomes in univariable analysis, but associations with most outcomes were lost after adjustment for conventional risk factors. The increase in P-ETP over time was greater with increasing albuminuria stage (p < 0.0001) and was independently associated with the kidney endpoints (p < 0.03). In the placebo arm, the increase in P-ETP was prognostic for all-cause mortality (HR [95% CI]; 1.14 [1.05–1.23], p = 0.003). Whereas levels of P-ETP were not impacted by treatment, levels of U-ETP significantly increased with canagliflozin treatment.ConclusionsP-ETP generated during COL VI formation predicts cardiovascular, kidney and mortality outcomes in patients with type 2 diabetes. As ETP identifies patients at increased risk of experiencing relevant outcomes, it may be used for patient enrichment in future clinical trials.Trial Registry Number (ClinicalTrials.gov Identifier): NCT01032629

Statistical models for the deterioration of kidney function in a primary care population: A retrospective database analysis.

Background: Evidence for kidney function monitoring intervals in primary care is weak, and based mainly on expert opinion. In the absence of trials of monitoring strategies, an approach combining a model for the natural history of kidney function over time combined with a cost-effectiveness analysis offers the most feasible approach for comparing the effects of monitoring under a variety of policies. This study aimed to create a model for kidney disease progression using routinely collected measures of kidney function. Methods: This is an open cohort study of patients aged ≥18 years, registered at 643 UK general practices contributing to the Clinical Practice Research Datalink between 1 April 2005 and 31 March 2014. At study entry, no patients were kidney transplant donors or recipients, pregnant or on dialysis. Hidden Markov models for estimated glomerular filtration rate (eGFR) stage progression were fitted to four patient cohorts defined by baseline albuminuria stage; adjusted for sex, history of heart failure, cancer, hypertension and diabetes, annually updated for age. Results: Of 1,973,068 patients, 1,921,949 had no recorded urine albumin at baseline, 37,947 had normoalbuminuria (<3mg/mmol), 10,248 had microalbuminuria (3-30mg/mmol), and 2,924 had macroalbuminuria (>30mg/mmol). Estimated annual transition probabilities were 0.75-1.3%, 1.5-2.5%, 3.4-5.4% and 3.1-11.9% for each cohort, respectively. Misclassification of eGFR stage was estimated to occur in 12.1% (95%CI: 11.9-12.2%) to 14.7% (95%CI: 14.1-15.3%) of tests. Male gender, cancer, heart failure and age were independently associated with declining renal function, whereas the impact of raised blood pressure and glucose on renal function was entirely predicted by albuminuria. Conclusions: True kidney function deteriorates slowly over time, declining more sharply with elevated urine albumin, increasing age, heart failure, cancer and male gender. Consecutive eGFR measurements should be interpreted with caution as observed improvement or deterioration may be due to misclassification.

Statistical models for the deterioration of kidney function in a primary care population: A retrospective database analysis

Background: Evidence for kidney function monitoring intervals in primary care is weak, and based mainly on expert opinion. In the absence of trials of monitoring strategies, an approach combining a model for the natural history of kidney function over time combined with a cost-effectiveness analysis offers the most feasible approach for comparing the effects of monitoring under a variety of policies. This study aimed to create a model for kidney disease progression using routinely collected measures of kidney function. Methods: This is an open cohort study of patients aged ≥18 years, registered at 643 UK general practices contributing to the Clinical Practice Research Datalink between 1 April 2005 and 31 March 2014. At study entry, no patients were kidney transplant donors or recipients, pregnant or on dialysis. Hidden Markov models for estimated glomerular filtration rate (eGFR) stage progression were fitted to four patient cohorts defined by baseline albuminuria stage; adjusted for sex, history of heart failure, cancer, hypertension and diabetes, annually updated for age. Results: Of 1,973,068 patients, 1,921,949 had no recorded urine albumin at baseline, 37,947 had normoalbuminuria (<3mg/mmol), 10,248 had microalbuminuria (3–30mg/mmol), and 2,924 had macroalbuminuria (>30mg/mmol). Estimated annual transition probabilities were 0.75–1.3%, 1.5–2.5%, 3.4–5.4% and 3.1–11.9% for each cohort, respectively. Misclassification of eGFR stage was estimated to occur in 12.1% (95%CI: 11.9–12.2%) to 14.7% (95%CI: 14.1–15.3%) of tests. Male gender, cancer, heart failure and age were independently associated with declining renal function, whereas the impact of raised blood pressure and glucose on renal function was entirely predicted by albuminuria. Conclusions: True kidney function deteriorates slowly over time, declining more sharply with elevated urine albumin, increasing age, heart failure, cancer and male gender. Consecutive eGFR measurements should be interpreted with caution as observed improvement or deterioration may be due to misclassification.

Prescribing pattern of Antihypertensive, Anti-Diabetic, Hypolipidaemic and Anti-Obesity Drugs in Diabetic Nephropathy

Objective: The Purpose of this study is to evaluate prescribing pattern of drugs to prevent progression of nephropathy in patients of diabetes in a tertiary care hospital. Materials and Methods: It was conducted in a tertiary care hospital, written informed consent was taken from those patients, who fulfilled study criteria and study sample included type 2 diabetic nephropathy outdoor patients who aged more than 40 years who were in stage of micro albuminuria (stage 3 diabetic nephropathy), details like sex, duration of illness, on-going treatment concurrent medicines were recorded in predesigned and pretested case record forms, these data were subjected to analysis using descriptive methods, Microsoft excel was used for data entry and descriptive analysis. A total of 100 patients were included in the study. A written permission has been obtained from Institutional Ethics Committee for the conduct of the study. Results: In the present study there were 100 patients, of whom 63 were males and 37 were females, majority of patients have diabetes for more than 20 years, all patients received anti-hypertensive, anti-diabetic and hypolipidaemic drugs. Among antihypertensive drugs, ACE inhibitors are prescribed most followed by diuretics and calcium channel blockers, among ACE inhibitors; Enalapril and Ramipril were prescribed most. Insulin was prescribed in 50% of patients and Glimepiride was the most common sulfonylurea prescribed. Statins were prescribed most among hypolipidaemic drugs; orlistat was prescribed only for 5% of patients. Majority of the patients were advised by physician regarding regular exercise, protein restricted diet, salt restriction, avoidance of cigarette smoking and weight reduction. Conclusion: Our study concluded that prescribing pattern of drugs in diabetic nephropathy was as per current practices and recommendations of guidelines. The pattern of drug use was to achieve better control of all the risk factors which are involved in progression of nephropathy. Further large scale and more detailed study, which includes sample from government setup and private clinics, is recommended to confirm our findings

Concomitant treatment with insulin and sodium–glucose cotransporter 2 inhibitors was associated with the renal composite outcome in Japanese patients with type 2 diabetes and chronic kidney disease: A propensity score‐matched analysis

ABSTRACTAims/IntroductionWe previously reported that sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment was associated with an improvement of the albumin‐to‐creatinine ratio in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. The present study clarified how concomitant insulin treatment (IT) with SGLT2i therapy influences the renal composite outcome (RCO).Materials and MethodsWe retrospectively evaluated 624 Japanese patients with type 2 diabetes mellitus and chronic kidney disease who underwent SGLT2i treatment. The renal composite outcome was set as progression of the stage of albuminuria or a ≥15% decrease in the estimated glomerular filtration rate per year. We developed a cohort model of patients managed with and without IT (Ins [+], Ins [−]) using propensity score matching methods. Furthermore, all patients in our study population were stratified into quintiles according to their propensity score.ResultsThe incidence of the RCO was in Ins (+) patients significantly higher than that in Ins (−) (P = 0.033). The estimated hazard ratio for the RCO was 1.55 (P = 0.035) in Ins (+) patients. The change in the estimated glomerular filtration rate and albumin‐to‐creatinine ratio in the groups was not statistically significant. The analysis, which was based on the quintiles, showed a statistically significant difference between the Ins (+) and Ins (−) groups (P = 0.01); the odds ratio for the RCO in patients managed with IT was 2.20 (P = 0.01).ConclusionsConcomitant administration of IT with SGLT2is influenced the RCO in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. We might need to consider the influence of concomitant agents on the renoprotective effects of SGLT2i therapy.

Association Between Serum Homocysteine Levels and Severity of Diabetic Kidney Disease in 489 Patients with Type 2 Diabetes Mellitus: A Single-Center Study.

BackgroundThis study from a single center aimed to investigate the association between serum homocysteine (Hcy) levels and severity of diabetic kidney disease (DKD) in 489 patients with type 2 diabetes mellitus (T2DM).Material/MethodsA total of 1163 patients with T2DM, including 674 T2DM without kidney disease (T2DM group) and 489 T2DM with DKD (DKD group), were evaluated. The DKD group was subdivided according to the chronic kidney disease (CKD) and albuminuria staging criteria in “Kidney Disease: Improving Global Outcomes 2012 clinical practice guideline” to quantify the severity of DKD: CKD stage 1 (n=164), CKD stage 2 (n=103), CKD stage 3 (n=95), CKD stage 4 (n=71), and CKD stage 5 (n=56) and stage A1 (n=57), stage A2 (n=250), and stage A3 (n=182), respectively. Peripheral blood was collected after 8 hours of fasting to test Hcy levels.ResultsIn CKD stages, Hcy levels gradually increased with increasing DKD severity (CKD stage 1 to 5); while in albuminuria stages, Hcy levels did not gradually increase with increasing DKD severity (stage A1 to A3). Hcy was an independent risk factor for CKD stages 2–5 (P<0.05), and had no effect on the albuminuria stages (P>0.05), while it may indirectly affect the occurrence of albuminuria stages through its impact on estimated glomerular filtration rate.ConclusionsThe relationship between Hcy level and DKD severity was related to the different staging methods used. Hcy was an independent risk factor for CKD stages but not albuminuria stages.

MO008: Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) without a Clear Family History have Rapid Progression and Poor Prognosis

Abstract BACKGROUND AND AIMS A small percentage of patients with autosomal dominant polycystic kidney disease (ADPKD) have no clear family history. The clinical course and prognosis of the disease in this subgroup of patients may be different. The present study investigates the progression and prognostication of end-stage renal disease (ESRD) in a large cohort of patients with and without a family history of ADPKD. METHOD This study enrolled 291 patients who were being followed in a specialized outpatient ADPKD clinic. Patients having a total of more than 10 kidney cysts in a recent magnetic resonance imaging (MRI) scan were included in the study even if they had no clear family history or confirmatory genetic test. At enrollment, total kidney volume was calculated by MRI, and the Mayo Clinic Imagining Category (MCIC) was determined. The prediction of ESRD (future estimated-glomerular filtration rate [e-GFR &amp;lt; 10 mL/min] based on the Mayo Clinic formula (which takes into consideration age, TKV, e-GFR, gender, race and MCIC) was also calculated. Demographics, medical and laboratory data were recorded using a standardized form. T-test, x2 and Mann–Whitney test were used for statistical analysis. RESULTS Of the 291 patients included in the study, 34 (11.68%) had no clear family history of ADPKD, and 257 (88.32%) had a clear family history. Age, gender, presence or not, and age at diagnosis of hypertension as well as BMI were similar in the two groups (P = 0.369, 0.398, 0.170, 0.295, 0.597, respectively). The age at diagnosis of ADPKD was similar between patients with and without a clear family history (P = 0.125) as well as, the e-GFR, the stage of chronic kidney disease and albuminuria (P = NS). The TKV tended to be higher in patients without a clear family history (median, [range]), 2210.3 (440.7–9137.5) mL versus 1649.9 (215.7–10 425.9) mL in those with a family history of ADPKD (P = 0.09), and the same was valid for the height-adjusted TKV (P = 0.08). In MCIC 1C, 1D and 1E, more patients without a known family history of ADPKD were classified than patients with a family history of ADPKD (88.89% versus 70.14%), and vice versa in MCIC 1A and 1B (11.11% versus 29.86%; P = 0.04). Finally, the ESRD prediction was (median, [range]) 15.66 (1–42) years for the patients without a clear family history and 34.1 (1–346) years for those with a clear family history of ADPKD (P = 0.025). CONCLUSION Patients with ADPKD without a clear family history tend to have a more rapid progression and a worse renal prognosis than those with a clear family history of the same disease.

Soluble tumor necrosis factor receptor 2 is associated with progressive diabetic kidney disease in patients with type 2 diabetes mellitus.

Chronic low-grade inflammation is considered one of the major mechanisms for the progression of diabetic kidney disease. We investigated the prognostic value of circulating soluble tumor necrosis factor receptor 2 (sTNFR2) for early nephropathy in patients with type 2 diabetes. A total of 364 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 were followed up for a median of 4 years. Renal outcomes were defined as a composite of either or both a >30% decline in the eGFR and/or albuminuria stage progression determined with consecutive tests. Seventy-three patients developed renal composite events. Serum concentrations of sTNFR2 were strongly associated with the risk of renal function decline and progressive changes in albuminuria. Through a receiver operating characteristic curve analysis, a serum sTNFR2 level of 1.608 ng/mL was adopted as the discriminator value for predicting renal outcomes (area under the curve 0.63, 95% confidence interval 0.57-0.70, p < 0.001), yielding a sensitivity of 75.3% and a specificity of 51.2%. The association of sTNFR2 levels ≥1.608 ng/mL to renal outcomes was significant after adjusting for relevant variables (hazard ratio 2.27, 95% confidence interval 1.23-4.20, p = 0.009) and remained consistent across subgroups stratified by age, sex, systolic blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system blockers. Higher circulating levels of sTNFR2 are independently associated with an eGFR decline and progressive albuminuria in patients with type 2 diabetes.

IDF21-0084 Role of serum copeptin levels in Type II Diabetes Mellitus patients with progressive stages of diabetic nephropathy

Background: Type II Diabetes mellitus (DM) is one of the leading metabolic diseases. It has multiple serious complications. Diabetic nephropathy is one of them. Progressive deterioration in renal functions due to DM makes the patient’s life completely handicapped. Thus, patients start depending on dialysis and ultimately develop its complications. Arginine Vasopressin (AVP) maintains glucose hemostasis and therefore, plays an important role in the pathophysiology of DM and its related complications such as diabetic nephropathy. Copeptin is an inactive analogue of AVP and considered as a reliable surrogate biomarker of AVP. Therefore, it is hypothesized that changes in the levels of copeptin can be correlated with diabetic and renal markers and thus may have potential role in predicting progressive stages of DM and diabetic nephropathy. Aim: The aim of the study is to find out the relation of copeptin with different diabetic and renal function biomarkers and to find out a potential role of copeptin as a predictive biomarker in DM and its associated progressive diabetic nephropathy. Method: It was a comparative cross-sectional study. A total number of 120 individuals were recruited into four groups i.e. controls, pre- diabetes, DM without nephropathy and DM with nephropathy as per the criteria of American Diabetes Association (ADA) 2018 and National Kidney Foundation/ Kidney Disease Outcome Quality Initiative (NKF/ KDOQI) 2018 guidelines. All cases were controlled hypertensive. Serum copeptin levels were measured by sandwich ELISA. While, Blood Urea Nitrogen (BUN), creatinine, Glycosylated Hemoglobin (HbA1c), urine micro albumin (UAE) and urinary creatinine were got done using spectrophotometry on Abbott Architect c8000 and electrolytes (Na+, K+ and Cl−) by iso electric method from Dow Diagnostic Research and Reference Laboratory (DDRRL), Dow University of Health Sciences. Statistical analysis was done using Analysis of Variance (ANOVA) and Pearson’s correlation tests on SPSS. Confounders were controlled using univariate linear regression. Results: The average copeptin levels of the study population were 215.096 pg/ml. Copeptin levels were significantly elevated in subjects with positive family history of DM (p = 0.025), levels were also raised in pre diabetes patients (252.85pg/ml) as compared to other groups. Copeptin levels were positively correlated with HbA1c r=0.171 (p=0.101), urea r=0.244 (p=0.007), creatinine r=0.215 (p=0.018), UAE r=0.310 (p=0.001), UACR r=0.375 (p=< 0.001). No significant correlation of copeptin was found with major electrolytes of the body. However, copeptin is found to be significantly associated with progressive stages of albuminuria and declining Glomerular Filtration Rate (GFR). Discussion: The raised levels of copeptin in subjects with positive family history of DM recommends its role in the early prediction of DM. Moreover, significant association of copeptin with progressive stages of albuminuria and declining GFR suggest the contribution of copeptin in the worsening of renal functions in DM and its associated nephropathy.

Serum klotho and its associations with blood and urine cadmium and lead across various stages of glomerular function: data for US adults aged 40-79years.

Exposures to cadmium and lead can cause oxidative stress, leading to tissue damage resulting in kidney and cardiovascular diseases. The antiaging protein klotho, on the other hand, is known to act as an anti-oxidative agent. How klotho homeostasis interacts with exposure to cadmium and lead has not been reported. Thus, this study was carried to investigate associations of serum klotho with blood and urine cadmium and lead in US adults aged 40-79years across stages of eGFR-based kidney function and albuminuria defined as urinary albumin/creatinine ratio of > 30mg/g creatinine. As long as the kidney function was normal (eGFR ≥ 90mL/min/1.73 m2) or near normal (60 ≤ eGFR < 90mL/min/1.73 m2), there was no evidence of an association between cadmium exposure and klotho concentrations irrespective of the presence/absence of albuminuria. During kidney dysfunction (15 ≤ eGFR < 60mL/min/1.73 m2), 10% increases in blood cadmium concentrations resulted in decreases in klotho concentrations between 0.27 and 0.84%. In addition, during severe kidney dysfunction (15 ≤ eGFR < 45mL/min/1.73 m2), a positive association between urine cadmium and serum klotho concentrations was observed. In the absence of albuminuria and when kidney function was normal or near normal, 10% increases in blood lead concentrations were observed to be associated with modest decreases between 0.28% and 0.37% in serum klotho concentrations. Similar results were observed between the concentrations of urine lead and serum klotho during kidney dysfunction.

A new era of diabetic kidney disease treatment with sodium-glucose cotransporter-2 inhibitors.

SGLT2 inhibitors may have a potential to stop the decline of renal function independent of the stage of albuminuria in diabetic kidney disease, and can be a new light in the post-RAS inhibitor era.

Abstract 10694: Relationship of Serum Triglycerides with Incident End Stage Renal Disease Across Urine Albumin-to-Creatinine Ratio Subgroups and Chronic Kidney Disease Stages

Background: Studies investigating serum triglycerides (TG) and renal outcomes including ESRD were mixed, and often these studies were unable to account for potential confounding for MetS components. It remains unclear how these relationships may present in patients with diabetic kidney disease and in consideration of albuminuria, or UACR. Methods: We studied 138,675 US diabetic veterans, with data on serum TG and UACR from 2004-2006 and follow-up until 2014. Using Cox models adjusted for clinical characteristics and laboratory markers (including UACR, body mass index, hemoglobin A1c and high-density lipoprotein), we evaluated the relationship of baseline TG with time to ESRD. All models were stratified by baseline CKD stage and baseline albuminuria stage ascertained at time of TG measurement. Results: The cohort was 65±11 years old, and included 28% with CKD 3A-5, and 4% with UACR &gt;300 mg/g. The median[IQR] of TG was 146[99,217] mg/dL. In non-albuminuric patients, we observed a linear relationship between TG and transition to ESRD among non-CKD patients, yet a U-shaped relationship for CKD 3A-3B (ref: TG 120-&lt;160 mg/dL). The relationship with TG ≥ 240 mg/dL diminished across CKD stages, where it was attenuated for CKD 4/5 patients (p-trend =0.05). In microalbuminuria patients, a trend towards an elevated risk of ESRD transition for TG ≥ 240 mg/dL was observed in CKD 3A and 4/5 only. Finally, patients with macroalbuminuria and elevated TG did not have a clear pattern in risk of ESRD across CKD stages (p-trend= 0.73). [Figure] Conclusion: In patients with diabetes and CKD, high TG levels predicted ESRD in CKD 3A non-albuminuria patients and in CKD 3A and 4/5 in patients with microalbuminuria. These associations were independent of glycemic control, MetS components, and medications including lipid-lowering drugs. These findings highlight the importance of investigating the impact of lipid modulating therapies specifically among patients with diabetic kidney disease.

Waist-Height Ratio and the Risk of Severe Diabetic Eye Disease in Type 1 Diabetes: A 15-Year Cohort Study.

ContextObesity prevalence has increased in type 1 diabetes (T1D). However, the relationship between body composition and severe diabetic eye disease (SDED) is unknown.ObjectiveTo investigate the associations between body composition and SDED in adults with T1D.MethodsFrom 5401 adults with T1D in the Finnish Diabetic Nephropathy Study, we assessed 3468, and 437 underwent dual-energy X-ray absorptiometry for body composition analysis. The composite outcome was SDED, defined as proliferative retinopathy, laser treatment, antivascular endothelial growth factor treatment, diabetic maculopathy, vitreous hemorrhage, and vitrectomy. Logistic regression analysis evaluated the associations between body composition and SDED. Multivariable Cox regression analysis assessed the associations between the anthropometric measures and SDED. Subgroup analysis was performed by stages of albuminuria. The relevance ranking of each variable was based on the z statistic.ResultsDuring a median follow-up of 14.5 (interquartile range 7.8-17.5) years, 886 SDED events occurred. Visceral/android fat ratio was associated with SDED [odds ratio (OR) 1.40, z = 3.13], as well as the percentages of visceral (OR 1.80, z = 2.45) and android fat (OR 1.28, z = 2.08) but not the total body fat percentage. Waist-height ratio (WHtR) showed the strongest association with the SDED risk [hazard ratio (HR) = 1.28, z = 3.73], followed by the waist (HR 1.01, z = 3.03), body mass index (HR 1.03, z = 2.33), and waist-hip ratio (HR 1.15, z = 2.22). The results were similar in normo- and microalbuminuria but not significant in macroalbuminuria. A WHtR ≥ 0.5 increased the SDED risk by 28% at the normo- and microalbuminuria stages.ConclusionsWHtR, a hallmark of central obesity, is associated with SDED in individuals with T1D.

Frequency and Correlation of Serum Uric Acid to Different Stages of Albuminuria in Type II Diabetic Nephropathy

Background: Albuminuria is considered the gold standard of onset and progression of diabetic nephropathy (DN). Higher levels of serum insulin may decrease uric acid clearance by the kidneys leading to hyperuricemia, which has injurious effect on kidneys. Objective: To evaluate the frequency and relationship of uric acid to different levels of albuminuria in type II diabetes mellitus. Patients and Method: This cohort study included 56 T2DM patients classified according to stages of DN into: Group I that including 12 patients with normoalbuminuria, group II included 26 patients with microalbuminuria, and group III including 18 patients with macroalbuminuria. All of them were evaluated for serum creatinine and albumin, CBC, ACR, UAE, HbA1c, ESR, Serum TSH and serum uric acid (SUA). Results: Hyperurecemia frequency was (62.5%) and it had highly statistical significant difference with albuminuria in the three studied groups. There was strong significant positive correlation of SUA with UAE (p < 0.014), Cr (p < 0.037), ACR (p < 0.006), HbA1c (p < 0.017) in macroalbuminuria and UAE (p < 0.042) and ACR (p < 0.043) in microalbuminuria group, and TLC (p < 0.024) in normoalbuminuria group. While there was a significant negative correlation between UA with albumin (p < 0.029) in macroalbuminuria group. Conclusions: Hyperinsulinemia and chronic inflammation associated with type IIDM leads to hyperuricemia, which had high frequency in our study (62.5%) and carry a hazardous effect on kidney function contributing to progressive increase of albuminuria. So we must search for management of elevated UA in these patients to delay onset & progression of its morbidity.

Costs and Healthcare Resource Use Associated with Risk of Cardiovascular Morbidity in Patients with Chronic Kidney Disease: Evidence from a Systematic Literature Review.

IntroductionThe management of chronic kidney disease (CKD) costs in excess of $114 billion in the USA and £1.45 billion in the UK annually and is projected to increase alongside the increasing disease prevalence. The aim of this review was to evaluate the risks of cardiovascular (CV) morbidity, CV mortality or all-cause mortality based on KDIGO (Kidney Disease: Improving Global Outcomes) 2012 categorisations and estimate the additional costs and healthcare resource utilisation associated with CV morbidity linked to CKD severity in US and UK settings.MethodsA systematic literature review was conducted of studies reporting on the risk of CV morbidity, CV mortality or all-cause mortality characterised by CKD severity (published between January 2000 and September 2018). Additional costs and bed days associated with CKD severity in the USA and UK were estimated on the basis of median hazard ratios for CV morbidity risk at each CKD and albuminuria stage.ResultsTwenty-nine studies reported risk of adverse clinical outcomes based on KDIGO categorisations. Compared to stage 1 (or without) CKD, patients with stage 5 CKD and macroalbuminuria experienced a relative risk increase of 11.77–12.46 across all outcomes. Additional costs and bed days associated with stage 5 CKD and macroalbuminuria (versus stage 1 (or without) CKD) per 1000 patient years were US$3.93 million and 803 bed days and £435,000 and 1017 bed days, in the USA and UK, respectively.ConclusionRisks of adverse clinical outcomes increase with CKD and albuminuria severity and are associated with substantial additional costs and resource utilisation. Thus, early diagnosis and proactive management of CKD and its complications should be a priority for healthcare providers to alleviate the burden of CV morbidity and its management on healthcare resources.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-020-01607-4.

Comparison of Two Different Semiquantitative Urinary Dipstick Tests with Albumin-to-Creatinine Ratio for Screening and Classification of Albuminuria According to KDIGO. A Diagnostic Test Study.

Background: Semiquantitative dipstick tests are utilized for albuminuria screening. Methods: In a prospective cross-sectional survey, we analyzed the diagnostic test validity of the semiquantitative colorimetric indicator-dye-based Combur9-Test® and the albumin-specific immunochromatographic assay Micral-Test® for the detection of albuminuria, the distribution of the semiquantitative measurements within the albuminuria stages according to KDIGO, and the utility for albuminuria screening compared with an albumin-to-creatinine ratio (ACR) in a walk-in population. Results: In 970 subjects, albuminuria (≥30 mg/g) was detected in 12.7% (95% CI 85.6–96.3%) with the ACR. Sensitivity was 82.9% (95% CI 75.1–89.1%) and 91.9% (95% CI 88.7–96.9%) and specificity 71.5% (95% CI 68.4–74.6%) and 17.5% (95% CI 15.0–20.2%) for the Combur9-Test® and Micral-Test®, respectively. Correct classification to KDIGO albuminuria stages A2/A3 with the Combur9-Test® was 15.4%, 51.4%, and 87.9% at cut-offs of 30, 100, and ≥300 mg/dL, and with the Micral-Test® it was 1.8%, 10.5%, and 53.6% at cut-offs of 2, 5, and 10 mg/dL, respectively. Overall, disagreement to KDIGO albuminuria was seen in 27% and 73% with the Combur9-Test® and Micral-Test®, respectively. From the total population, 62.5% and 15.3% were correctly ruled out and 2.2% and 1% were missed as false-negatives by the Combur9-Test® and Micral-Test®, respectively. Conclusion: Compared to the Combur9-Test®, the utility of the Micral-Test® is limited, because the fraction of correctly ruled out patients is small and a large proportion with a positive Micral-Test® require a subsequent ACR conformation test.

Cross-sectional and longitudinal associations between dipstick hematuria and chronic kidney disease in patients with type 2 diabetes

AimsTo examine the association of dipstick hematuria with kidney function and albuminuria in patients with type 2 diabetes (T2D). MethodsA total of 7,945 patients with T2D were studied. In the cross-sectional study, patients were classified into 6 groups based on the stage of albuminuria and estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 at baseline. In the longitudinal study where patients were classified by the presence of hematuria, the primary composite endpoint was a 30% decrease in eGFR from baseline or the initiation of kidney replacement therapy. Other outcomes included eGFR slope and stage progression of albuminuria. ResultsCross-sectionally, hematuria was more prevalent in patients with more advanced stages of albuminuria and with lower eGFR, independently of each other. In the longitudinal study, patients with hematuria experienced 50% increased incidence of the primary endpoint (p < 0.001). The eGFR slope was steeper in patients with hematuria than in those without hematuria (p < 0.001). On the other hand, hematuria was unlikely to be associated with the progression of albuminuria. ConclusionsIn patients with T2D, dipstick hematuria was associated with prevalent albuminuria and reduced eGFR, as well as faster decline in kidney function but not higher risk of development or progression of albuminuria.

Acute Kidney Injury: A Bona Fide Complication of Diabetes.

The landscape of kidney disease in diabetes has shifted. The classical dogma of "diabetic nephropathy" progressing through stages of albuminuria, leading to decline in glomerular filtration rate and end-stage kidney disease (ESKD), has been replaced by a more nuanced understanding of the complex and heterogeneous nature of kidney disease in diabetes. Paralleling this evolution, standardized definitions have resulted in a growing appreciation that acute kidney injury (AKI) is increasing in its incidence rapidly and that people with diabetes are much more likely to develop AKI than people without diabetes. Here, I propose that AKI should be considered a complication of diabetes alongside other complications that similarly do not fit neatly into the historical microvascular/macrovascular paradigm. In this article, we take a look at the evidence indicating that diabetes is a major risk factor for AKI and we review the causes of this increased risk. We consider the long-term implications of AKI in diabetes and its potential contribution to the future development of chronic kidney disease, ESKD, and mortality. Finally, we look toward the future at strategies to better identify people at risk for AKI and to develop new approaches to improve AKI outcomes. Recognizing AKI as a bona fide complication of diabetes should open up new avenues for investigation that may ultimately improve the outlook for people living with diabetes and at risk for kidney disease.

Elabela levels in patients with type 2 diabetes: can it be a marker for diabetic nephropathy?

Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative correlation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=-0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbuminuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients.

P1005LONG NONCODING RNAS MAY INTERVENE IN PODOCYTE INJURY AND PROXIMAL TUBULE DYSFUNCTION THROUGH MODULATING MIRNAS EXPRESSION IN EARLY DIABETIC KIDNEY DISEASE OF TYPE 2 DIABETES MELLITUS PATIENTS

Abstract Background and Aims Interactions among multiple molecules and signalling pathways contribute to the pathogenesis and progression of diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aim of the study was to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients. The molecular mechanisms of lncRNAs intervention were evaluated in relation to a particular miRNA profile. Method A total of 136 patients with type 2 DM and 25 healthy subjects were enrolled in a cross-sectional case series study and assessed concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), and urinary miRNA21, 124, 93, 29a (quantified by a real-time PCR System). Results Multivariable regression analysis yielded models in which urinary lncRNA MALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93 and 29a (p&amp;lt;0.0001; R2=0.727); urinary lncRNA NEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, and 29a (p&amp;lt;0.0001; R2=0.702); urinary lncRNA MIAT correlated directly with miRNA93 and 29a, and eGFR (p&amp;lt;0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, and 124 (p&amp;lt;0.0001; R2=0.654); urinary lncRNA TUG1 correlated directly with eGFR, miRNA93 and 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, and 124 (p&amp;lt;0.0001; R2=0.748). The results provided document upregulated lncRNA MALAT1 and NEAT1, as well as miRNA21 and 124. By contrast, lncRNA MIAT and TUG1, and miRNA93 and 29a were downregulated. Conclusion In patients with type 2 DM lncRNAs exert distinct functions in different cell types, either deleterious or protective, at both glomerular and tubular level. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.