Persistent Microalbuminuria Research Articles

Association of MnSOD (rs4880) and GPx1 (rs1050450) with diabetic nephropathy: a meta-analysis

Abstract Background Microvascular complications of diabetes including retinopathy, nephropathy, and neuropathy are those long-term complications that affect small blood vessels. Diabetic nephropathy (DN) is characterized by persistent microalbuminuria. A meta-analysis of case–control studies aims to examine the relationship between MnSOD (rs4880) and GPx1 (rs1050450) and the risk of DN. Methods Various databases such as Web of Science, PubMed, Springer Link, Cochrane Library, Science Direct, Embase, and Google Scholar were utilized to extract relevant studies. The statistical software MedCalc version 22.009 was acquired to accomplish the meta-analysis of the included studies. Results A significant association was found between two SNPs (rs4880 and rs1050450) and DN in the homozygous recessive model [95% confidence interval (CI) 0.97–2.41, odds ratio (OR) TT vs CC = 1.53, P = 0.06] and heterozygous model [95% CI 0.92–1.97, OR CT vs CC = 1.35, P = 0.12], while there was no association with the other genetic models. A significant association between rs4880 and DN was perceived in the Asian population [95% CI 1.24–2.03, OR = 1.6, P < 0.001], meanwhile the studies among Caucasian group showed insignificant association [95% CI 0.87–1.32, OR = 1.07, P = 0.5]. On the other hand, the association between rs1050450 and DN was significant [95% CI 3.80–13.01, OR = 7.04, P < 0.001] and insignificant [95% CI 0.96–2.28, OR = 1.48, P = 0.07] among Asian and Caucasian population, respectively. Conclusion To date, this meta-analysis could be the first to contribute a panoramic exploration of the MnSOD and GPx1 polymorphic association with DN. The results of the study contemplate the data presently accessible from the literature and can be employed as an influential lead for future research.

The development and progression of albuminuria in South Asians with type 2 diabetes compared with Western Europeans. Results from the HinDu the Hague diabetes study.

Although South Asians have an increased risk to develop diabetes, data on the difference in development and progression of diabetic nephropathy between ethnic groups are not consistent. The aim of this study was to evaluate possible differences in the development and progression of albuminuria in South Asians and Western Europeans (WE) with type 2 diabetes in a large closed cohort of South Asians with type 2 diabetes. Data on 1269 South Asians and 2272 Dutch adults with type 2 diabetes who were treated in our diabetes clinic in 2006 or referred thereafter were extracted from electronic medical records. Microalbuminuria and macroalbuminuria were defined separately for men and women based on albumin/creatinine ratios in early morning urine samples. We defined 3 outcomes: (1) no albuminuria, (2) persistent microalbuminuria and (3) macroalbuminuria at the end of follow-up. Cox proportional hazard models were used to discriminate differences in time from diabetes diagnosis until development and progression of albuminuria between the two ethnic groups, adjusted for retinopathy, hypertension, smoking and age at diabetes diagnosis. South Asians have a higher adjusted risk for developing microalbuminuria: HR 1.4, (95% CI 1.2, 1.6) and macroalbuminuria: HR: 1.2 (1.0, 1.4) compared to Western Europeans. However, mean time to progress from micro- to macroalbuminuria was not different between the ethnic groups (3.9 ± 4.0 yrs vs. 3.4 ± 3.9 yrs respectively). South Asians have a higher adjusted risk to develop micro- and macroalbuminuria compared with Western Europeans. When microalbuminuria is present, time to progression from micro- to macroalbuminuria is not different between the two groups.

Correlation of Kidney Injury Molecule-1 and Nephrin Levels in Iraqi Patients with Diabetic Nephropathy

Background: Diabetic nephropathy is characterized by persistent microalbuminuria and metabolic changes that decline renal functions. Researchers have been prompted to explore new biomarkers such as KIM-1 and nephrin that may enhance the identification of disease. Objective: To Evaluate biomarker levels of kidney injury molculre-1 (KIM-1) concentration and nephrin as early and sensitive markers of nephropathy in type 2 diabetic patients. Method: One hundred T2DM patients were included in a cross-sectional study at the specialized center for endocrinology and diabetes, Baghdad. The first group includes 50 diabetic nephropathy (DN) patients, and the second group includes 50 T2DM patients without DN. Biochemical and clinical parameters were reported for participants, and serum and urine levels of KIM-1 and nephrin were analyzed by Enzyme-linked immunosorbent assay. Results: The study showed a significant increase in serum and urinary levels of KIM-1 and nephrin in DN patients compared to the control group. Serum nephrin is positively correlated with urinary nephrin, serum creatinine, ACR ratio, serum and urine KIM-1, and negatively correlated with the estimated glomerular filtration rate. Urinary nephrin was positively correlated with urinary albumin/creatinine ratio, KIM-1 level in both serum and urine, and negatively correlated with estimated glomerular filtration rate. Conclusion: KIM-1 and nephrin are specific and sensitive indicators of early-stage diabetic nephropathy-associated renal damage.

Microalbuminuria in Perinatally HIV-Infected Children and Adolescents in the United States.

The kidney is a common target for human immunodeficiency virus (HIV), making renal disease a common noninfectious complication of HIV. Microalbuminuria is an important marker that can detect early renal damage. Timely detection of microalbuminuria is important to initiate renal management and stop the progression of renal dysfunction in people with HIV. Limited data are available about renal abnormalities in people with perinatal HIV infection. The objective of this study was to determine the prevalence of microalbuminuria in a cohort of perinatally HIV-infected children and young adults receiving combination antiretroviral therapy and investigate correlations between microalbuminuria and clinical and laboratory findings. This was a retrospective study of 71 patients with HIV followed in an urban pediatric HIV clinic in Houston, Texas, between October 2007 and August 2016. Demographic, clinical, and laboratory data were compared between subjects with persistent microalbuminuria (PM) and those without. PM is defined as a microalbumin-to-creatinine ratio ≥30 mg/g on at least 2 occasions separated by at least 1 month. Sixteen of 71 patients (23%) met the definition of PM. In univariate analysis, patients with PM had significantly higher CD8+ T-cell activation and lower CD4+ T-cell nadir. Multivariate analysis demonstrated increased microalbuminuria to be independently associated with older age and CD8+ T-cell activation measured as CD8+HLA-DR+ T-cell percentage. Older age and increased activation of CD8+HLA-DR+ on T cells correlate with presence of microalbuminuria in this cohort of HIV-infected patients.

#5482 CIRCULATING BIOMARKERS OF COLLAGEN REMODELING AS MARKERS FOR DEVELOPMENT OF MICROALBUMINURIA IN TYPE 2 DIABETES: THE PRIORITY TRIAL

Abstract Background and Aims Kidney disease progression is characterized by extensive deposition of extracellular matrix components such as collagen. Therefore, we assessed the effect of spironolactone on collagen remodeling biomarkers and investigated the association between the markers and development of microalbuminuria in serum of persons with type 2 diabetes and normoalbuminuria. Method We measured collagen type III (PRO-C3), VI (PRO-C6; endotrophin), VII (PRO-C7), and XXVIII (PRO-C28) formation, and a fragment of degraded crosslinked collagen type III (CTX-III) in serum of persons with high-risk (stratified by a urinary proteomics classifier, CKD273) for development of microalbuminuria, randomized to either spironolactone 25 mg or placebo. Crude and adjusted Cox models were applied to investigate the association between baseline biomarker levels and development of the primary outcome, persistent microalbuminuria, and development of microalbuminuria in at least one morning void sample, used as a secondary outcome. Results In the PRIORITY trial, spironolactone treatment did not prevent progression to microalbuminuria compared to placebo. All biomarkers were measured in 154 participants at baseline and 117 at end-of-study (week 208). Treatment with spironolactone did not affect serum levels of any of the investigated collagen remodeling biomarkers compared to placebo, and there were no differences in delta-biomarker levels between baseline and end-of-study (p ranging 0.277-0.875). In crude analyses, serum endotrophin was associated with both the primary (n = 44) and secondary outcome (n = 74) (HR per two-fold higher level: 1.58, 95% CI: 1.03-2.44, p = 0.037 and 1.62, 1.12-2.35, p = 0.010), whereas serum PRO-C3 was only associated with the secondary outcome (1.89, 1.19-2.99, p = 0.007). After adjustment for sex, baseline age, systolic blood pressure, estimated glomerular filtration rate, urinary albumin-creatinine ratio, and HbA1c, serum endotrophin and PRO-C3 remained significantly associated with the secondary outcome (1.52, 1.03-2.24, p = 0.036 and 1.73, 1.08-2.78, p = 0.022). Levels of PRO-C7, PRO-C28, and CTX-III were not associated with the specified outcomes. Neither baseline levels of serum endotrophin nor PRO-C3 correlated with baseline CKD273 levels (R: 0.00-0.06, p>0.47). Conclusion Treatment with spironolactone did not change serum levels of collagen remodeling biomarkers. Serum endotrophin, reflecting collagen type VI formation and the pro-fibrotic molecule endotrophin, and PRO-C3, a marker of collagen type III formation, were associated with development of microalbuminuria in at least one urine sample, suggesting that these biomarkers are relevant risk markers for kidney disease development in type 2 diabetes.

Prevalence of LDL-hypercholesterolemia and other cardiovascular risk factors in young people with type 1 diabetes

BackgroundMortality and morbidity in people with Type 1 diabetes (T1D) is mainly caused by cardiovascular disease (CVD). Early treatment of cardiovascular risk factors (CVRFs) is of great importance. ObjectiveTo analyze the prevalence of LDL-hypercholesterolemia and other CVRFs in youth with T1D. MethodsClinical and laboratory parameters, and vascular thickness measurement were obtained in youth with T1D (age 6-18 years, T1D duration >1 year) attending a diabetes clinic. LDL-hypercholesterolemia, microalbuminuria and arterial hypertension were defined as CVRFs. ResultsA total of 333 youth (48% girls; age: 13.3 years [10.3-15.5], median [interquartile range]) participated in the study. The T1D duration was 5.9 years [3.5-9.4] with HbA1c of 7.4% [6.8-8.0]. Intima media thickness (N=223) was 538.0 µm [470.0-618.0]). LDL-hypercholesterolemia was present in 30 participants (9%; 18 girls; age: 14.3 years [11.2-15.7]). None of the participants had persistent microalbuminuria, although 59 (18.3%) had elevated albumin excretion in a random urine specimen. LDL-hypercholesterolemia was associated with increased blood pressure (p<0.05), insulin requirement (p<0.05), HbA1c (p<0.05), triglyceride (p<0.001) and total cholesterol (p<0.001), and a family history of premature CVD (p<0.001), but negatively correlated with HDL cholesterol levels (p<0.05). Sex, pubertal status, duration of diabetes, type of therapy, and physical activity did not differ between participants with and without LDL- hypercholesterolemia. Arterial hypertension was present in 11 participants (3.3%; 4 girls; age: 14.1 years [11.1-16.1]). ConclusionLDL-hypercholesterolemia affected 9% of youth with T1D in this cohort and was associated with other CVRFs. A holistic therapeutic concept for these young people is essential.

Presence of retinopathy and incident kidney and cardiovascular events in type 2 diabetes with normoalbuminuria – A post-hoc analysis of the PRIORITY randomized clinical trial

AimsBaseline diabetic retinopathy (DR) and risk of development of microalbuminuria, kidney function decline, and cardiovascular events (CVEs) in type 2 diabetes. MethodsPost-hoc analysis of the PRIORITY study including 1758 persons with type 2 diabetes and normoalbuminuria followed for a median of 2.5 (IQR: 2.0–3.0) years. DR diagnosis included non-proliferative and proliferative abnormalities, macular oedema, or prior laser treatment. Cox models were fitted to investigate baseline DR presence with development of persistent microalbuminuria (urinary albumin-creatinine ratio > 30 mg/g); chronic kidney disease (CKD) G3 (eGFR <60 ml/min/1.73m2); and CVE. Models were adjusted for relevant risk factors. ResultsAt baseline, 304 (17.3 %) had DR. Compared to persons without DR, they were older (mean ± SD: 62.7 ± 7.7 vs 61.4 ± 8.3 years, p = 0.019), had longer diabetes duration (17.9 ± 8.4 vs. 10.6 ± 7.0 years, p < 0.001), and higher HbA1c (62 ± 13 vs. 56 ± 12 mmol/mol, p < 0.001). The adjusted hazard ratios of DR at baseline for development of microalbuminuria (n = 197), CKD (n = 166), and CVE (n = 64) were: 1.50 (95%CI: 1.07, 2.11), 0.87 (95%CI: 0.56, 1.34), and 2.61 (95%CI: 1.44, 4.72), compared to without DR. ConclusionsPresence of DR in normoalbuminuric type 2 diabetes was associated with an increased risk of developing microalbuminuria and CVE, but not with kidney function decline.

Evaluation and risk factors of microalbuminuria in children with type 1 diabetes in Aswan University Hospital

Background Diabetic nephropathy is the major complication of diabetes and is one of the leading causes of end-stage renal disease. Early identification of nephropathy is crucial to slow down this process. Assessment of albuminuria is used as an early clinical marker for impaired kidney function. The aim of this study is to evaluate the magnitude of microalbuminuria (MA) in children with type 1 diabetes and determine the factors correlated to it. Patients and methods A cohort study that was carried out on diabetic children attained the endocrinology clinic in our hospital from August 2019 to October 2020. Children aged 6–18 years old with a history of 2 years of diabetes were subjected to history, examination, and investigation, including urea, creatinine, lipid profile, hemoglobin A1c, and 24-h urinary albumin were done twice. Statistical analysis used χ 2, Fisher exact, and independent Wilcoxon t test for comparison between groups. Spearman and Pearson's for correlations. Results The median (interquartile range) of MA in the first visit was 10 mg/24 h (6.15–20 mg/24 h) in the first visit versus 9.5 mg/24 h (4.9–23.55 mg/24 h) in the second visit, with an insignificant P value. The abnormal numbers of hemoglobin A1c in the first visit were 85.7 and 79.3% in the second visit; P value is 0.350. Children with abnormal MA were 13.2% in the first visit versus 20% in the second visit with only four patients having persistent MA. MA was positively correlated to the Tanner stage in the first visit to blood pressure, serum triglyceride, and Tanner stage in the second visit, and negatively correlated to high-density lipoprotein. Conclusion Most of our patients had uncontrolled diabetes with an increasing prevalence of MA over time.

Urinary C-megalin as a novel biomarker of progression to microalbuminuria: A cohort study based on the diabetes Distress and Care Registry at Tenri (DDCRT 22)

AimsMegalin is a multiligand receptor expressed in proximal tubular cells that reabsorbs filtered albumin and correlates cross-sectionally with albuminuria. We investigated the association between urinary C-megalin levels and the incidence of microalbuminuria in patients with diabetes mellitus. MethodsThis cohort study included 752 patients with type 1 or 2 diabetes mellitus and a urinary albumin-to-creatinine (Cr) ratio (UACR) within the normoalbuminuric range (<30 mg/g Cr). The association between urinary C-megalin and persistent microalbuminuria, accounting for the possible interaction between baseline UACR and urinary C-megalin, was estimated using a Cox proportional hazards model. ResultsDuring a median follow-up period of 1.99 years, 179 cases of persistent microalbuminuria were observed. The association between urinary C-megalin and persistent microalbuminuria was UACR-dependent (P for interaction < 0.001), with the highest association observed in the absence of UACR (per 100 fM/gCr of urinary C-megalin: adjusted hazard ratio, 1.13; 95% CI 1.07–1.19), gradually decreasing as UACR increased to 30 mg/g Cr. UACR dependence was confirmed by sensitivity analyses according to low-normal (<10 mg/gCr) or high-normal (10–<30 mg/gCr) UACR. ConclusionsUrinary C-megalin is associated with progression to microalbuminuria, especially in those with low-normal UACR levels, and its usefulness to identify high risk patients requires further investigation.

Clinical Applications of Microalbuminuria

Microalbuminuria is a marker for generalized vascular dysfunction. Persistent microalbuminuria indicates a high probability of damage to the glomerular filtration capacity of the kidney and is of great diagnostic relevance. Albuminuria has also been shown more recently to be a predictor of cardiovascular outcomes. Emerging data that reduces albuminuria leads to reduced risk of adverse renal and cardiovascular events, and steps should be taken to suppress albuminuria to prevent future renal and cardiovascular adverse events. This review discusses the measurement of albuminuria and summarizes the current literature on the association between albuminuria and adverse cardiovascular and renal outcomes in type 2 diabetes and hypertension.

Pre-eclampsia is a valuable opportunity to diagnose chronic kidney disease: a multicentre study.

ABSTRACTBackgroundPre-eclampsia (PE) and chronic kidney disease (CKD) are known to be associated. Our objective was to assess the prevalence of CKD in a large multicentre cohort of women without acknowledged CKD who experienced a PE episode.MethodsThe setting for the study was France (Le Mans, Central France) and Italy (Cagliari, Sardinia). The study participants were patients who experienced PE in 2018–19, identified from the obstetric charts. Patients with known–acknowledged CKD were excluded. Only singletons were considered. Persistent (micro)albuminuria was defined as present and confirmed at least 3 months after delivery. CKD was defined according to the Kidney Disease Outcomes Quality Initiative guidelines; urinary alterations or low eGFR confirmed at a distance of at least 3 months, or morphologic changes. Patients were divided into four groups: evidence of CKD; no evidence of CKD; unclear diagnosis-ongoing work-up; or persistent microalbuminuria. The outcome ‘diagnosis of CKD’ was analysed by simple and multiple logistic regressions. Temporal series (week of delivery) were analysed with Kaplan–Meier curves and Cox analysis.ResultsTwo hundred and eighty-two PE pregnancies were analysed (Le Mans: 162; Cagliari: 120). The incidence of CKD diagnosis was identical (Le Mans: 19.1%; Cagliari: 19.2%); no significant difference was found in unclear-ongoing diagnosis (6.2%; 5.8%) and microalbuminuria (10.5%; 5.8%). Glomerulonephritis and diabetic nephropathy were more frequent in Cagliari (higher age and diabetes prevalence), and interstitial diseases in Le Mans. In the multivariate logistic regression, CKD diagnosis was associated with preterm delivery (adjusted P = 0.035). Gestation was 1 week shorter in patients diagnosed with CKD (Kaplan–Meier P = 0.007). In Cox analysis, CKD remained associated with shorter gestation after adjustment for age and parity.ConclusionsThe prevalence of newly diagnosed CKD is high after PE (19% versus expected 3% in women of childbearing age), supporting a systematic nephrology work-up after PE.

Series: Cardiovascular outcome trials for diabetes drugs Semaglutide and SUSTAIN-6

SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes) was a pre-licensing FDA-mandated cardiovascular outcome trial with subcutaneous semaglutide and was the first completed trial with a once-weekly glucagon-like peptide-1 receptor agonist. SUSTAIN-6 compared semaglutide and placebo in 3,297 people with type 2 diabetes and established cardiovascular disease, chronic kidney disease, or both, or who were aged over 60 years and had subclinical evidence of cardiovascular disease (persistent microalbuminuria or proteinuria, hypertension with left ventricular hypertrophy, left ventricular dysfunction by imaging, ankle/brachial index less than 0.9). As SUSTAIN-6 was performed as a pre-licensing safety study, non-inferiority for major cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) was the primary outcome and testing for superiority for MACE was not pre-specified or adjusted for multiplicity. SUSTAIN-6 confirmed non-inferiority for MACE, with nominal superiority, and demonstrated a significant reduction in the risk of non-fatal stroke. There was no significant difference in non-fatal myocardial infarction, cardiovascular death, all-cause mortality or hospitalisation for heart failure. Rates of retinopathy complications were unexpectedly higher in the semaglutide group. Further outcome trials with subcutaneous semaglutide are in progress, including a cardiovascular outcome trial in non-diabetic subjects with overweight or obesity.

STUDY ON REDUCTION OF MICROALBUMINURIA AMONGST HYPERTENSIVE PATIENTS WITH USE OF TRIPLE COMBINATION THERAPY (TRIPLIXAM)

Objective: Persistent microalbuminuria is earliest indicator of Chronic Kidney Disease amongst hypertensive patients and is also associated with target organ damage resulting in stroke, retinopathy and adverse cardiovascular outcomes. The present study was aimed to evaluate the reduction in microalbuminuria amongst uncontrolled essential hypertensive patients with use of triple combination therapy. Design and method: It was a hospital based cross sectional prospective study done on 50 essential hypertension patients having uncontrolled blood pressure and presence of microalbuminuria in urine. Total duration of therapy was 3 months and triple combination therapy used in study as antihypertensive was Triplixam (Perindopril 4 mg, Amlodipine 5 mg and Indapamide 1.25 mg). Patients having Diabetes and other co morbidities were excluded from the study. Patients were evaluated at baseline and end of study visit for SBP,DBP, Urine for albumin excretion. Ethical clearance was taken prior to inclusion of patients. Results: There was significant reduction in both SBP (18 mm Hg) and DBP (10 mm Hg) with use of triple combination therapy (Triplixam). Microalbuminuria turned to normal albumin excretion in urine that was statistically significant (p &lt; 0.01) was most significant and convincing finding. Conclusions: Triplixam is an excellent triple agent that can reduce blood pressure promptly and bring about reduction in urine albumin excretion thereby decreasing risk of end target organ damage. Early detection of renal dysfunction through microalbuminuria and prompt treatment can confer future protection from end stage renal disease.

Role of Nrf2 dysfunction in the pathogenesis of diabetic nephropathy: Therapeutic prospect of epigallocatechin-3-gallate

Diabetic nephropathy (DN), a progressive kidney disease afflicts more than 20 and up to 40% of the diabetic population and it is characterized by persistent microalbuminuria declined glomerular filtration rate. The interesting feature associated with DN is that, even though the progression of the disease correlates with oxidative stress, Nrf2, the master regulator of antioxidant defense system involved in counteracting oxidative stress is also upregulated in the diabetic kidneys of both human as well as experimental animals in early stages of DN. Despite the increased expression, the ability of this protein to get translocated into the nucleus is diminished signifying the functional impairment of Nrf2, implying redox imbalance. Hence, it is understood that agents that boost the translocation of Nrf2 might be beneficial rather than those that quantitatively overexpress Nrf2 in treating DN. The deleterious effects of synthetic Nrf2 activators have instigated the researchers to search for phytochemicals that have ambient Nrf2 boosting ability with no side effects, one such phytochemical is Epigallocatechin-3-gallate (EGCG) and it has shown beneficial effects by preventing the progression of DN via influencing Nrf2/ARE pathway, however, the modus operandi is unclear, despite speculations. This study was designed to find out whether supplementation of Nrf2 booster like EGCG at the crucial time of Nrf2 dysfunction can mitigate the progression of DN. Based on the findings of the present study, it might be concluded that the beneficial effect of EGCG in mitigating DN is mediated mainly through its ability to activate the Nrf2/ARE signaling pathway at multiple stages i.e., by downregulating Keap1 and boosting the nuclear Nrf2 level by disrupting Nrf2-Keap1 interaction. These results emphasize that supplementation of EGCG might be more beneficial at an early stage of DN, where dysfunctional Nrf2 accumulation occurs, which should be further validated.

Diabetic neuropathy and other diabetic complications at the Diabetic Neuropathy Center of the University of Debrecen

The prevalence of diabetes mellitus is significantly increasing worldwide. Distal sensorimotor neuropathy (DSPN) is the most common and the earliest detectable microvascular complication. Due to its diverse clinical appearance and atypical symptoms, DSPN is often recognized in an advanced stage. In our study, the data of 431 patients who were examined using the Neurometer® between 2011 and 2018 at the Diabetic Neuropathy Center of the University of Debrecen were processed and the correlations between cardiovascular and microvascular complications, laboratory parameters and the severity of DSPN were investigated. The average age of patients was 63.4 years, 62% of them were women, and 92% had type 2 diabetes mellitus. The average duration of diabetes was 13.7 years. Cardiovascular disease (CVD) was diagnosed in 42% of the patients. The incidence of retinopathy was 12%, persistent microalbuminuria was 16%. Despite DSNP complaints, neuronal damage could not be detected in 19%; in the examined patients 49% had mild, 19% moderate and 13% severe neuropathy. Diabetes-related neurological damage was more serious in the presence of both diabetic retinopathy (p<0.001) and microalbuminuria (p<0.001). The incidence of these microvascular complications and the severity of DSPN showed a significant positive correlation (p<0.001). There was no correlation between the severity of peripheral neuropathy and the development of CVD, and we did not find any correlations between the severity of DSPN and CVD. Based on our investigation, correlation between the progression of diabetic neuropathy and cardiovascular complications was not found, although the progression of diabetic neuropathy indicated the development of other microvascular diseases. Peripheral neurological examination using the Neurometer® is appropriate for controlling the DSPN status and the establishment of the severity of neuropathy determines the quality of life in diabetic patients. Among these patients, the risk of CVD can be assessed by Ewing's test for autonomic nervous system function. Orv Hetil. 2020; 161(30): 1243-1251.

P1006IMPACT OF GLUCOSE-LOWERING AND ANTIHYPERTENSIVE MEDICATIONS ON DEVELOPMENT OF MICROALBUMINURIA IN SUBJECTS WITH TYPE 2 DIATETES AND NORMOALBUMINURIA IN THE PRIORITY STUDY

Abstract Background and Aims In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. In this sub-study, we aim to evaluate whether glucose-lowering and antihypertensive medications, many of which have been demonstrated to have albuminuria-lowering effects, may interfere with the predictive value of CKD273. Method A post hoc analysis of a prospective observational study with embedded randomised placebo-controlled trial. Setting 1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years). Patients Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score &amp;gt; 0.154). Main outcome measures Baseline medication or initiation during the study was assessed for the following medications: glitazones, glucagon-like peptide-1 receptor agonists (GLP1-RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), angiotensin-converting-enzyme inhibitors (ACEi), angiotensin-II-receptor blockers (ARB), calcium channel blockers (CCB) and beta blockers (BB). The main outcome was development of confirmed microalbuminuria (urinary albumin to creatinine ratio (UACR) &amp;gt;30 mg/g and with ≥30% increase from baseline) in 2 of 3 consecutive samples. Results The hazard ratio (HR (95% CI)) for development of microalbuminuria (high vs. low-risk) was 3.9 (2.9-5.3) in a crude Cox-model; and 2.4 (1.8-3.4; p&amp;lt;0.0001) when adjusted for age, sex, HbA1c, systolic blood pressure, retinopathy, eGFR and UACR. Adding baseline medications to the model did not significantly alter the results. When evaluating medications initiated during the study, more high- than low-risk subjects were started on glitazones, GLP1-RA, SGLT2i, CCB and BB (p&amp;lt;0.03), however, only initiation of DPP4i was associated with the outcome. Adjustment for DPP4i initiated during the study did not significantly change the HR for development of confirmed microalbuminuria (HR 2.5 (1.8 to 3.4); p&amp;lt;0.0001) in a model including eGFR and UACR. The HR for development of persistent microalbuminuria (spironolactone vs. placebo) was 0.81 (0.49-1.34; p=0.41), however, adjusting for DPP4i did not significantly alter this result. Conclusion Although several glucose-lowering and antihypertensive medications were more frequently prescribed in high-risk subjects, the CKD273 classifier prospectively predicted confirmed microalbuminuria, independent of baseline co-medications and medication initiated during the study. Moreover, initiated medications during the study could not explain the inability of spironolactone to delay progression to microalbuminuria.

Evaluation of urinary L-FABP as an early marker for diabetic nephropathy in type 2 diabetic patients.

Albuminuria is the standard biomarker for the diagnosis of diabetic nephropathy (DN). However, some patients with persistent microalbuminuria still progress to chronic kidney disease, raising the question of finding a better biomarker. This study aimed to evaluate the correlation of urinary liver-type fatty acid-binding protein (L-FABP) levels with renal function and to compare the role of urinary albumin-to-creatinine ratio (ACR) with urinary L-FABP in early detection of DN in type 2 diabetic patients. The cross-sectional study was done on 106 type 2 diabetic patients and 30 non-diabetic people. L-FABP was measured with the Latex enhanced immunoturbidimetric technique. There was a strong and negative correlation between the urine L-FABP levels and eGFR (r = -0.606, p<0.001). The urinary L-FABP levels were significantly higher (p<0.001) in the normoalbuminuria diabetic group than the non-diabetic control group. The ROC-curve analyses in the diabetic patients and the normoalbuminuria diabetic patients showed that the AUCL-FABP was remarkably higher (p<0.001) than the AUCACR. An optimal cutoff value of 5 mg L-FABP/g Cr (with the sensitivity of 98.1% and specificity of 90%) and of 4.3 mg L-FABP/g Cr (with the sensitivity of 100% and specificity of 86.67%) was set to detect DN in the diabetic patients and the normoalbuminuria diabetic patients, respectively. The change in urinary L-FABP levels happened earlier than in urinary albumin during renal function impairment. Urinary L-FABP can be used as a better indicator than ACR for early detection of DN in type 2 diabetes.

Is preeclampsia a risk for end-stage renal disease?

Little information is available about the risk of end-stage renal disease (ESRD) after preeclampsia. The review of Covella etal. demonstrated that former preeclamptic women have a significant risk of ESRD in the medium term. However, it is still unknown which preeclamptic woman are at higher risk for progressive kidney disease. After delivery, women who had preeclampsia, particularly those with persistent hypertension, symptomatic proteinuria, or microalbuminuria, should receive a regular checkup for kidney disease.

Expression of exosomal miR-21 and miR-29 in serum of children and adolescents with T1DM and persistent microalbuminuria

BackgroundAlthough microalbuminuria is the earliest marker for DN, its presence is not necessarily linked to DN diagnosis or progression in some patients. Therefore, the factors that play a role in the pathogenesis of DN must be clarified, especially in juvenile-onset T1DM patients. Aim of studyWe aimed to investigate expression of serum exosomal miR-21 and miR-29 in children and adolescents with T1DM and persistent microalbuminuria. Subjects and MethodsExosomal miR-21 and miR-29 were assayed in serum of 120 T1DM patients (60 with normoalbuminuria and 60 with persistent microalbuminuria) and 60 healthy subjects using quantitative reverse transcriptase PCR (qRT PCR). ResultsExpression of miR-21 and miR-29 was significantly elevated in patients with or without microalbuminuria than in controls (p = 0.02, 0.0 and 0.001, 0.006) with no significant difference in miR-21 level between the two patients' groups. Expression of miR-29 was significantly elevated in patients with microalbuminuria compared to patients without microalbuminuria (p = 0.003). Confirmation of association of miR-29 with T1DM and persistent microalbuminuria was done using regression analysis after adjustment of age, sex, BMI, disease duration, total cholesterol, triglycerides, HDL and LDL (p = 0.005, 0.01 respectively). ROC analysis showed miR-29 is a marker of persistent microalbuminuria (P = 0.003). ConclusionElevated expression of miR-29 may play a role in pathogenesis of T1DM and associated DN and might represent a potential biomarker for early diagnosis of diabetic nephropathy in pediatric patients and a future target for therapy.

Application of urinary proteomics as possible risk predictor of renal and cardiovascular complications in patients with type 2-diabetes and microalbuminuria

BackgroundAnalyses of the urinary proteome have been proposed as a novel approach for early assessment of increased risk of renal- or cardiovascular disease.Here we investigate the potentials of various classifiers derived from urinary proteomics for prediction of renal and cardiovascular comorbidities in patients with type 2-diabetes. MethodsThe study was a post hoc analysis of the randomized controlled Steno-2 trial comparing intensified multifactorial intervention to conventional treatment of type 2-diabetes and microalbuminuria. 151 diabetic patients with persistent microalbuminuria were included in year 1995 and followed for up to 19 years. For renal outcomes, two classifiers (CKD273 and a novel, GFR-based classifier) and for cardiovascular outcomes, three classifiers (CAD238, ACSP and ACSP75) were applied. Renal endpoints were progression to macroalbuminuria, impaired renal function (GFR < 45 ml/min/1.73 m2) or progression to end stage renal disease (ESRD) or death. Cardiovascular endpoints were coronary artery disease and a composite endpoint of incident death of cardiovascular disease, myocardial infarction or revascularization, stroke, amputation or peripheral revascularization. ResultsCKD273 was not consistently associated with renal outcomes. The GFR-based classifier was associated with impaired renal function, but lost significance in extensively adjusted models. Both the ACSP75 and ACSP-scores, but not the CAD238-score were inversely associated (opposing the hypothesis) with cardiovascular endpoints. None of the classifiers improved prediction of any outcome on top of standard risk factors. ConclusionsRisk-scores based upon urinary proteomics did not improve prediction of renal and cardiovascular endpoints on top of standard risk factors such as age and GFR during long-term (19 years) follow up in patients with type 2-diabetes and microalbuminuria.