Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE).

BACKGROUND: Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and an SGLT2i is superior to either agent alone. METHODS: CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicenter, three-armed, parallel-group, 7.5 - to 8.5-month, Phase 2 study in 807 adults with T2D, stage 2-3 CKD and a urine albumin:creatinine ratio (UACR) ≥300-<5000 mg/g. The primary objective is to demonstrate that 6 months of dual therapy comprising finerenone and the SGLT2i empagliflozin is superior for reducing albuminuria versus either agent alone. Interventions will be once-daily finerenone 10 mg or 20 mg (target dose) plus empagliflozin 10 mg, or empagliflozin 10 mg alone, or finerenone 10 mg or 20 mg (target dose) alone. RESULTS: The primary outcome is a relative change from baseline in UACR among the three groups. Secondary outcomes will further characterize efficacy and safety, including changes in estimated glomerular filtration rate and incident hyperkalemia. CONCLUSIONS: CONFIDENCE is evaluating the safety, tolerability and efficacy of dual use of finerenone and an SGLT2i in adults with CKD and T2D. Should an additive effect be shown, early and efficient intervention with dual finerenone and SGLT2i therapy could slow disease progression and provide long-term benefits for people with CKD and T2D.

Predictors of microalbuminuria and its relationship with glycemic control among Type 2 diabetic patients of Jazan Armed Forces Hospital, southwestern Saudi Arabia.

BACKGROUND AND PURPOSE: Diabetic kidney disease (DKD) is highly prevalent among patients with diabetes mellitus. It affects approximately 20% of diabetic patients, who are believed to be more than 400 million individuals. The objectives of the present work were to assess patterns of albuminuria and determine microalbuminuria predictors among patients living with type 2 diabetes (T2D) who attended the family medicine department of Jazan Armed Forces Hospital. METHODS: A case-control design was used and included two groups (n, 202/group), one with microalbuminuria and the other with a normal urine albumin/creatinine ratio (ACR). Data regarding patient history, glycosylated hemoglobin (HbA1c), lipid profile, renal function tests, ACR, ASCVD (atherosclerotic cardiovascular disease) risk, etc., were collected. RESULTS: The prevalence rates of microalbuminuria and macroalbuminuria were 26.4% and 3.9%, respectively. HbA1c was significantly higher in patients with microalbuminuria (9.3 ± 2.2; P˂0.001) and macroalbuminuria (10.5 ± 2.3; P˂0.001) than in those with normal ACR (8.3 ± 1.9%). The predictors of microalbuminuria were poor glycemic control with HbA1c ≥ 7% {OR, 2.5 (95% C. I, 1.5-4.2)}; hypertension {(OR, 1.8 (95% C. I, 1.2-2.8)}; estimated glomerular filtration rate (eGFR) of ˂90 mL/min/1.73 m2 {OR, 2.2 (95% C. I, 1.4-3.6}; smoking {OR, 1.3 (95% C. I, 0.7-2.6}; and body mass index {OR, 1.05 (95% C. I, 1.01-1.09}. CONCLUSION: Microalbuminuria is highly prevalent among patients with type 2 diabetes and is associated with poor glycemic control and hypertension, necessitating aggressive and timely screening and treatment.

Efficacy and safety of esaxerenone (CS-3150) in Japanese patients with type 2 diabetes and macroalbuminuria: a multicenter, single-arm, open-label phase III study.

BACKGROUND: Esaxerenone has potential renoprotective effects and reduces the urinary albumin-to-creatinine ratio (UACR) in patients with diabetic kidney disease and overt nephropathy. We investigated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes (T2D) and macroalbuminuria (UACR ≥ 300 mg/g creatinine). METHODS: We conducted a multicenter, single-arm, open-label phase III study in 56 patients with T2D and UACR ≥ 300 mg/g creatinine with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and treated with a renin-angiotensin system inhibitor. Patients received esaxerenone for 28 weeks at 1.25 mg/day initially with titration to 2.5 mg/day based on serum potassium (K+) monitoring. Efficacy was evaluated as the change in UACR from baseline to week 28. Safety endpoints included adverse events (AEs), incidence of serum K+ increase, and change in eGFR from baseline. RESULTS: UACR decreased by 54.6% (95% CI 46.9%, 61.3%) on average from baseline (544.1 mg/g creatinine) to the end of treatment (246.8 mg/g creatinine); 51.8% of patients showed improvement to early nephropathy. AE incidence was 69.6%. Three patients (5.4%) had serum K+ levels ≥ 6.0 mEq/L or ≥ 5.5 mEq/L on two consecutive occasions. Hyperkalemia in two patients was transient and resolved during the treatment period. One patient discontinued following two consecutive serum K+ values ≥ 5.5 mEq/L. The maximum change from baseline in eGFR was - 8.3 mL/min/1.73 m2 at week 24. CONCLUSIONS: Esaxerenone reduced UACR in Japanese patients with T2D and UACR ≥ 300 mg/g creatinine; more than half experienced a transition from UACR ≥ 300 mg/g creatinine to UACR < 300 mg/g creatinine. CLINICAL TRIAL REGISTRATION: JapicCTI-173696.

Association between urinary salt excretion and albuminuria in Japanese patients with chronic kidney disease: the Fukuoka kidney disease registry study.

BACKGROUND: Several large population-based studies have demonstrated that urinary salt excretion (USALT) is associated with albuminuria. However, this relationship has not been assessed in a large cohort study of patients with chronic kidney disease (CKD). Thus, the present study aimed to elucidate whether USALT was independently associated with albuminuria in a large cohort of patients with CKD. METHODS: This cross-sectional study was conducted in 4075 patients with CKD not on dialysis. USALT (g/day) was estimated from spot urine. Patients were divided into quartiles (Q1-Q4) according to estimated USALT. Multivariable regression models were used to determine whether USALT was independently related to urinary albumin-to-creatinine ratio (UACR) or the presence of macroalbuminuria. RESULTS: In multivariable linear regression analyses, 1-g/day increment in USALT was significantly associated with log UACR [coefficient 0.098, 95% confidence interval (CI) 0.075-0.121]. In addition, compared with the first USALT quartile, the third and fourth quartiles exhibited significant associations with log UACR (Q3: coefficient 0.305, 95% CI 0.154-0.456; Q4: coefficient 0.601, 95% CI 0.447-0.756). Furthermore, multivariable logistic regression analyses showed that USALT (1-g/day increment) was significantly associated with the presence of macroalbuminuria [odds ratio (OR) 1.11, 95% CI 1.07-1.14]; the third and fourth USALT quartiles exhibited significantly greater risks of macroalbuminuria, compared with the first quartile (Q3: OR 1.33, 95% CI 1.09-1.62; Q4: OR 1.89, 95% CI 1.54-2.32). CONCLUSIONS: This significant association of USALT with UACR and macroalbuminuria suggests that higher USALT may cause increased albuminuria, thereby contributing to kidney disease progression.

Galectin-3 is independently associated with progression of nephropathy in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Galectin-3 has been implicated in cardiac and renal fibrosis and serves as a prognostic clinical indicator in heart failure. The aim of the present study was to evaluate whether serum galectin-3 level is associated with progressive kidney disease in type 2 diabetes. METHODS: Galectin-3 was measured in baseline samples by ELISA in 1320 participants with type 2 diabetes with eGFR ≥30 ml min-1 1.73 m-2. The primary outcome was defined as doubling of serum creatinine and/or initiation of renal replacement therapy during follow-up. The secondary outcome was progression to macroalbuminuria in individuals with normo- or microalbuminuria at baseline. RESULTS: Serum galectin-3 levels were significantly increased in a random subgroup of 270 type 2 diabetic individuals with eGFR >60 ml min-1 1.73 m-2 compared with an age- and sex-matched non-diabetic control group (7.58 ± 2.29 ng/ml vs 6.10 ± 1.91 ng/ml, respectively, p < 0.01). In the whole diabetic cohort, after a mean follow-up of 9 years, galectin-3 was independently associated with doubling of serum creatinine (HR 1.19; 95% CI 1.14, 1.24, p < 0.001) and incident macroalbuminuria (HR 1.20; 95% CI 1.12, 1.30, p < 0.001), even after adjusting for traditional risk factors, baseline eGFR and albuminuria status. Individuals with galectin-3 levels in the highest quartile had a fourfold risk of renal function loss and threefold risk of incident macroalbuminuria. CONCLUSIONS/INTERPRETATION: Serum galectin-3 was independently associated with progressive renal disease in type 2 diabetes. Further mechanistic studies are warranted to determine whether galectin-3 is simply a disease biomarker or is also a mediator of the development and progression of diabetic nephropathy.

Risk of Progression of Nonalbuminuric CKD to End-Stage Kidney Disease in People With Diabetes: The CRIC (Chronic Renal Insufficiency Cohort) Study.

BACKGROUND: Reduced glomerular filtration rate (GFR) in the absence of albuminuria is a common manifestation of chronic kidney disease (CKD) in diabetes. However, the frequency with which it progresses to end-stage kidney disease (ESKD) is unknown. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: We included 1,908 participants with diabetes and reduced GFR enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. PREDICTORS: Urinary albumin and protein excretion. OUTCOMES: Incident ESKD, CKD progression (ESKD or ≥50% reduction in estimated GFR [eGFR] from baseline), and annual rate of decline in kidney function. MEASUREMENTS: ESKD was ascertained by self-report and by linkage to the US Renal Data System. We used Cox proportional hazards modeling to estimate the association of albuminuria and proteinuria with incident ESKD or CKD progression and linear mixed-effects models to assess differences in eGFR slopes among those with and without albuminuria. RESULTS: Mean eGFR at baseline was 41.2mL/min/1.73m2. Normal or mildly increased 24-hour urinary albumin excretion (<30mg/d) at baseline was present in 28% of participants, but in only 5% of those progressing to ESKD. For those with baseline normal or mildly increased albuminuria, moderately increased albuminuria (albumin excretion, 30-299mg/d), and 2 levels of severely increased albuminuria (albumin excretion, 300-999 and ≥1,000mg/d): crude rates of ESKD were 7.4, 34.8, 78.7, and 178.7 per 1,000 person-years, respectively; CKD progression rates were 17.0, 61.4, 130.5, and 295.1 per 1,000 person-years, respectively; and annual rates of eGFR decline were -0.17, -1.35, -2.74, and -4.69mL/min/1.73m2, respectively. LIMITATIONS: We were unable to compare the results with healthy controls. CONCLUSIONS: In people with diabetes with reduced eGFRs, the absence of albuminuria or proteinuria is common and carries a much lower risk for ESKD, CKD progression, or rapid decline in eGFR compared with those with albuminuria or proteinuria. The rate of eGFR decline in normoalbuminuric CKD was similar to that reported for the general diabetic population.

Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on All-Cause Mortality and Renal Outcomes in Patients with Diabetes and Albuminuria: a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) could benefit patients with diabetes and albuminuria remains controversial. A systematic review and meta-analysis were conducted to answer this question by comparing ACE inhibitors or ARB with placebo among these patients. METHODS: In this meta-analysis, electronic data sources (Medline, the Cochrane Collaboration, and EMBASE) were searched. Randomized controlled trials (RCTs) comparing ACE inhibitors or ARB with placebo in subjects with diabetes and albuminuria (defined as urinary albumin-to-creatinine ratio, UACR≥30mg/g Cr) were included. Outcomes parameters were all-cause mortality, end stage renal disease (ESRD), doubling of serum creatinine levels, and cardiovascular events (CV). RESULTS: Twenty-six RCTs (including 20 for ACE inhibitors and 6 for ARB) were included, comprising 10378 participants with diabetes and albuminuria. Compared to placebo, treatment with ACE inhibitors or ARBs did not reduce all-cause mortality or CV. For renal outcomes, ARBs significantly reduced the risk of ESRD by 23% (odds ratio 0.77, 95%CI 0.65-0.92), while ACE inhibitors were not associated with a decreased risk of ESRD (0.69, 0.43-1.10). Both ACE inhibitors and ARBs reduced the risk of doubling of the serum creatinine level (0.60, 0.39-0.91 for ACE inhibitors; 0.75, 0.64-0.88 for ARBs), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results. CONCLUSION: In patients with diabetes and albuminuria, ARBs reduced risks of ESRD and doubling of the serum creatinine level. ACE inhibitors and ARBs failed to reduce all-cause mortality and CV. Based on the renoprotective effects, ARBs may be preferred for diabetic patients with albuminuria.

Decline in estimated glomerular filtration rate is associated with risk of end-stage renal disease in type 2 diabetes with macroalbuminuria: an observational study from JDNCS.

BACKGROUND: There is increased interest in surrogate endpoints for clinical trials of chronic kidney disease. METHODS: In this nationwide observational study of 456 patients with type 2 diabetes and clinically suspected diabetic nephropathy followed for a median of 4.2 years, we evaluated the association between estimated glomerular filtration rate (eGFR) and albuminuria at baseline or during follow-up and risk of ESRD. RESULTS: Low eGFR (<60 mL/min/1.73 m2) and macroalbuminuria at enrollment were independently associated with risk of ESRD. In patients with macroalbuminuria, both ≤-50% change and -50 to -30% change in eGFR over 1 and 2 years were predictive of ESRD. The higher cut point (≥50% decline in eGFR) was more strongly predictive but less common. Remission of macroalbuminuria to normo-/microalbuminuria at 1 and 2 years was associated with a lower incidence of ESRD than no remission; however, it was not a determinant for ESRD independently of initial eGFR and initial protein-to-creatinine ratio. CONCLUSION: These results suggest that a ≥30% decline in eGFR over 1 or 2 years adds prognostic information about risk for ESRD in patients with type 2 diabetes and macroalbuminuria, supporting the consideration of percentage decline in eGFR as a surrogate endpoint among macroalbuminuric cases in type 2 diabetes. On the other hand, our study suggests that additional analyses on the relationship between remission of macroalbuminuria and risk of ESRD are needed in type 2 diabetes.

Factors associated with diabetic nephropathy in children, adolescents, and adults with type 1 diabetes.

BACKBROUD/PURPOSE: Microalbuminuria and macroalbuminuria are markers of diabetic nephropathy (DN). The purpose of this study was to unravel the risk factors for DN in the young patients with type 1 diabetes (T1D). METHODS: 341 patients (160 males) with T1D diagnosed at the age 7.6 ± 4.0 years with disease duration 11.5 ± 6.5 years were assessed. Among them, 185 were young adults (aged 18.0-36.2 years). Urinary albumin creatinine ratio (UACR) was checked on morning spot urine. Microalbuminuria and macroalbuminuria were defined as a UACR of 30-300 mg/g and >300 mg/g, respectively, in at least 2 consecutive specimens. RESULTS: 50 (14.7%) patients were classified as microalbuminuria and 13 (3.8%) as macroalbuminuria. In all patients, multivariate logistic regression revealed that the most significant risk factors were average HbA1c (%), OR (95% CI) = 1.76 (1.37-2.25), P = 0.002); and male sex, OR = (odd ratio 2.31 (1.19-4.46), P = 0.013). In adult patients, the most significant factors were average HbA1c, OR = 1.74 (1.32-2.31), P = 0.003; and systolic blood pressure, OR = 1.06 (1.01-1.11), P = 0.011. Survival analysis showed average HbA1c levels significantly influenced the development of DN. CONCLUSION: The most important risk factors for DN were average HbA1c and age. When microalbuminuria is detected, proper treatment with ACEIs or ARBs and improving glycemic control can delay progression of DN.

The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Sodium glucose cotransporter 2 (SGLT2) inhibition lowers HbA1c, systolic BP (SBP) and weight in patients with type 2 diabetes and reduces renal hyperfiltration associated with type 1 diabetes, suggesting decreased intraglomerular hypertension. As lowering HbA1c, SBP, weight and intraglomerular pressure is associated with anti-albuminuric effects in diabetes, we hypothesised that SGLT2 inhibition would reduce the urine albumin-to-creatinine ratio (UACR) to a clinically meaningful extent. METHODS: We examined the effect of the SGLT2 inhibitor empagliflozin on UACR by pooling data from patients with type 2 diabetes and prevalent microalbuminuria (UACR = 30-300 mg/g; n = 636) or macroalbuminuria (UACR > 300 mg/g; n = 215) who participated in one of five phase III randomised clinical trials. Primary assessment was defined as percentage change in geometric mean UACR from baseline to week 24. RESULTS: After controlling for clinical confounders including baseline log-transformed UACR, HbA1c, SBP and estimated GFR (according to the Modification of Diet in Renal Disease [MDRD] formula), treatment with empagliflozin significantly reduced UACR in patients with microalbuminuria (-32% vs placebo; p < 0.001) or macroalbuminuria (-41% vs placebo; p < 0.001). Intriguingly, in regression models, most of the UACR-lowering effect with empagliflozin was not explained by SGLT2 inhibition-related improvements in HbA1c, SBP or weight. CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes and either micro- or macroalbuminuria, empagliflozin reduced UACR by a clinically meaningful amount. This effect was largely independent of the known metabolic or systemic haemodynamic effects of this drug class. Our results further support a direct renal effect of SGLT2 inhibitors. Prospective studies are needed to explore the potential of this intervention to alter the course of kidney disease in high-risk patients with diabetes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01177813 (study 1); NCT01159600 (study 2); NCT01159600 (study 3); NCT01210001 (study 4); and NCT01164501 (study 5).

Link between retinopathy and nephropathy caused by complications of diabetes mellitus type 2.

While the correlation and chronology of appearance of diabetic nephropathy and retinopathy is well known in diabetes mellitus (DM) type 1 patients, in DM type 2 this correlation is less clear. A retrospective study including 917 patients with type 2 diabetes. Diabetic retinopathy (DR) was diagnosed based on fundus photographs taken with a non-mydriatic camera. Diabetic nephropathy (DN) was diagnosed based on urinary albumin concentration in a morning urine sample. Statistical analysis was performed with a seemingly unrelated regression (SUR) model. Our SUR model is statistically significant: the test for "model versus saturated" is 2.20 and its significance level is 0.8205. The model revealed that creatinine and glomerular filtration rate (GFR) have strong influence on albuminuria, while body mass index (BMI) and HbA1c have less significant impact. DR is affected positively by diabetes duration, insulin treatment, glucose levels, and HbA1c, and it is affected negatively by GFR, triglyceride levels, and BMI. The association between DR and DN was statistically significant and had a unidirectional correlation, which can be explained by chronological order; that is, DN precedes DR. The present study indicates that the level of renal impairment is proportional to the level of damage to the eye. Furthermore, such an association has a chronological aspect; the renal injury precedes retinal damage.

Arteriolar Hyalinosis Predicts the Onset of Both Macroalbuminuria and Impaired Renal Function in Patients with Type 2 Diabetes.

INTRODUCTION: Arteriolar hyalinosis (AH) has been shown to be associated with albuminuria and GFR. In this study, we investigated whether or not index of AH (IAH) is a predictor of the onset of macroalbuminuria and impaired renal function (eGFR <60 mL/min/1.73 m2 [eGFR <60]) in type 2 diabetic patients with early diabetic nephropathy. METHODS: The study population consisted of 35 patients with type 2 diabetes (25 men; age: 47 ± 9 years; eGFR: 92.7 ± 18.0 mL/min/1.73 m2) with normo- or microalbuminuria who underwent percutaneous renal biopsy. These patients were followed for at least 5 (18 ± 6, range: 6-28) years. The study endpoint was the onset of macroalbuminuria or eGFR <60. Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate glomerular and interstitial structural changes. RESULTS: During the observation period, 9 out of the 35 patients progressed to macroalbuminuria, and 15 out of the 35 patients developed eGFR <60. The annual rate of eGFR decline was significantly correlated with IAH (r = -0.40, p = 0.016). Kaplan-Meier analysis demonstrated that AH was associated with a significantly higher risk of onset of macroalbuminuria and eGFR <60, and microalbuminuria is associated with the onset of macroalbuminuria but not the onset of eGFR <60. CONCLUSIONS: Aggravated AH is a histological risk factor which predicts the onset of macroalbuminuria and eGFR <60 in patients with type 2 diabetes. These findings provide novel insights into the mechanism of progression of diabetic nephropathy.

Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes.

Abnormalities of sphingolipid metabolism play an important role in diabetes. We compared sphingolipid levels in plasma and in isolated lipoproteins between healthy control subjects and two groups of patients, one with chronic kidney disease without diabetes (ND-CKD), and the other with type 2 diabetes and macroalbuminuria (D-MA). Ceramides, sphingomyelins, and sphingoid bases and their phosphates in LDL were higher in ND-CKD and in D-MA patients compared to controls. However, ceramides and sphingoid bases in HDL2 and HDL3 were lower in ND-CKD and in D-MA patients than in controls. Sphingomyelins in HDL2 and HDL3 were lower in D-MA patients than in controls but were normal in ND-CKD patients. Compared to controls, lactosylceramides in LDL and VLDL were higher in ND-CKD patients but not in D-MA patients. However, lactosylceramides in HDL2 and HDL3 were lower in both ND-CKD and D-MA patients than in controls. Plasma hexosylceramides in ND-CKD patients were increased and sphingoid bases decreased in both ND-CKD and D-MA patients. However, hexosylceramides in LDL, HDL2, and HDL3 were higher in ND-CKD patients than in controls. In D-MA patients, only C16:0 hexosylceramide in LDL was higher than in controls. The data suggest that sphingolipid measurement in lipoproteins, rather than in whole plasma, is crucial to decipher the role of sphingolipids in kidney disease.

Serum cell division cycle 42 reflects the development and progression of diabetic nephropathy in patients with diabetes mellitus.

Cell division cycle 42 (CDC42) regulates podocyte apoptosis to take part in the development and progression of diabetic nephropathy (DN), but currently the clinical evidence is limited. The aim of the present study was to investigate the capability of serum CDC42 expression level to estimate the development and progression of DN in patients with diabetes mellitus (DM). Patients with type 2 DM (n=306) were enrolled and divided into normoalbuminuria (n=185), microalbuminuria (n=72) and macroalbuminuria (n=49) groups based on the urinary albumin-to-creatinine ratio. Serum CDC42 was measured in all subjects using enzyme-linked immunosorbent assay. The median (interquartile range) CDC42 in patients with DM was 0.461 (0.314-0.690) ng/ml (range, 0.087-1.728 ng/ml). CDC42 was positively associated with the estimated glomerular filtration rate (P<0.001), but negatively correlated with body mass index, systolic blood pressure, hemoglobin A1c, serum creatine, serum uric acid and C reactive protein (all P<0.050). CDC42 levels were lowest in the macroalbuminuria group, followed by the microalbuminuria group, and were highest in the normoalbuminuria group (P<0.001). CDC42 indicated that it was a favorable estimator for the presence of albuminuria [area under the curve (AUC), 0.792; 95% confidence interval (CI), 0.736-0.848] and macroalbuminuria (AUC, 0.845; 95% CI, 0.775-0.915). By analyses in four different multivariate logistic regression models, increased CDC42 was independently associated with the presence of microalbuminuria (all P<0.001), macroalbuminuria (most P<0.001) and microalbuminuria + macroalbuminuria (all P<0.001). Serum CDC42 level negatively correlated with microalbuminuria and macroalbuminuria in patients with DM, suggesting its ability for estimating the development and progression of DN.

Diabetes mellitus, hypertension and albuminuria in rural Zambia: a hospital-based survey.

OBJECTIVE: To assess albuminuria in rural Zambia among patients with diabetes mellitus only (DM group), hypertension only (HTN group) and patients with combined DM and HTN (DM/HTN group). METHODS: A cross-sectional survey was conducted at St. Francis Hospital in the Eastern province of Zambia. Albumin-creatinine ratio in one urine sample was used to assess albuminuria. Other information obtained included age, sex, body mass index (BMI), waist circumference (WC), blood pressure (BP), glycosylated haemoglobin (HbA1c ), random capillary glucose, time since diagnosis, medication and family history of DM or HTN. RESULTS: A total of 193 participants were included (DM group: n = 33; HTN group: n = 92; DM/HTN group: n = 68). The participants in the DM group used insulin more frequently as diabetes medication than the DM/HTN group (P < 0.05). Furthermore, the DM group was younger and had lower BMI, WC and BP than the two other groups. In the DM group, HTN group and DM/HTN group, microalbuminuria was found in 12.1%, 19.6% and 29.4% (P = 0.11), and macroalbuminuria was found in 0.0%, 3.3% and 13.2% (P = 0.014), respectively. The urine albumin (P = 0.014) and albumin-creatinine ratio (P = 0.0006) differed between the three groups. CONCLUSION: This hospital-based survey in rural Zambia found a lower frequency of albuminuria among the participants than in previous studies of patients with DM or HTN in urban sub-Saharan Africa.

Prediction of hemorrhagic transformation in acute ischaemic stroke by micro- and macroalbuminuria after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is one of the most problematic complications to arise from intravenous thrombolysis (IVT). This study was conducted to assess whether micro- and macroalbuminuria could be associated with HT after IVT in patients with acute ischaemic stroke, and to investigate whether the value of urinary albumin-to-creatinine ratios would correlate with the degree of HT. METHODS: This was a retrospective study of stroke patients who had undergone IVT within 3 h of symptom onset. Albuminuria assessment was based on random morning spot urine collection with patients in a fasting state, the first morning after IVT. Multiple logistic regression analysis was used to evaluate whether the presence of micro- and macroalbuminuria might be independent predictors of HT. RESULTS: One-hundred and fifty-four patients were included in the study. Fifty-one patients had HT. The presence of micro- or macroalbuminuria was associated with HT after adjustment for variables with clinical significance (adjusting for age, atrial fibrillation, platelet counts, baseline National Institutes of Health Stroke Scale score, hypertension and diabetes mellitus; odds ratio, 2.542; 95% confidence interval, 1.106-5.841; P = 0.028). There were significant relationships between the presence of micro- and macroalbuminuria and types of HT. CONCLUSION: In conclusion, the results of this study suggest that the presence of micro- and macroalbuminuria after IVT could be a predictor of severe HT in patients with acute ischaemic stroke.

The Prevalence of Severely Increased Albuminuria in the Type 2 Diabetes Population with Chronic Kidney Disease of Low Socioeconomic Status in San Juan: A Population in Need of Improved Accessibility to Disease-Modifying Therapy.

OBJECTIVE: The aim of this study was to determine the prevalence of severely increased albuminuria and the percentage of patients with the indication for canagliflozin in the type 2 diabetes population with chronic kidney disease (CKD) and low socioeconomic status in the San Juan City Hospital. METHODS: This cross-sectional study examined the electronic records of 129 Hispanic type 2 diabetes patients. CKD in this population was defined according to the most recent nephrology and endocrinology guidelines. Albuminuria was diagnosed with two positive urine albumin/creatinine ratio results within 3-6 months. Data was obtained from July 2017 to January 2020 and analyzed utilizing descriptive statistics and correlations. RESULTS: The prevalence of moderately and severely increased albuminuria in patients with type 2 diabetes and CKD were 51.2% and 18.6% respectively. The number of patients with type 2 diabetes who filled the FDA indication for canagliflozin were 16.3%. The prevalence of hypertension, coronary artery disease (CAD) and heart failure (HF) was 61.2%, 15.5% and 10.1% respectively. Between albuminuria severity and decreased renal function, a tendency was observed although not statistically significant (r = -0.14, 95% CI: -0.31, 0.03; P = 0.109). While evaluating association between albuminuria groups and CAD, there was a noticeable tendency close to reaching statistical significance (P = 0.060). CONCLUSION: There is a scarcity of studies regarding the prevalence of severely increased albuminuria in type 2 diabetics with CKD and this study contributes to the literature. On analysis of associations, statistical significance not reached likely due to small sample size.

Expression of Angiopoetin-Like Protein-4 and Kidney Injury Molecule-1 as Preliminary Diagnostic Markers for Diabetes-Related Kidney Disease: A Single Center-Based Cross-Sectional Study.

The purpose of the study was to examine the urinary levels of kidney injury molecule-1 (KIM-1) and angiopoietin-like protein-4 (ANGPTL-4) in individuals with diabetic kidney disease (DKD) and their association with established DKD diagnostic markers such as albuminuria and estimated glomerular filtration rate (eGFR). Levels of ANGPTL-4 and KIM-1 were estimated in urine samples. A total of 135 participants were recruited into three groups: 45 diabetes type 2 patients in the control group and 90 DKD patients in two disease groups. Concentrations of ANGPTL-4 and KIM-1 were conclusively related to the urinary albumin-creatinine ratio (UACR). Also, the levels of both ANGPTL-4 and KIM-1 were negatively associated with the eGFR. Multivariable Poisson regression analysis showed that urinary ANGPTL-4 (PR: 3.40; 95% CI: 2.32 to 4.98; p < 0.001) and KIM-1 (PR: 1.25; 95% CI: 1.14 to 1.38; p < 0.001) were prevalent in DKD patients. Receiver operating characteristic (ROC) analysis of urinary ANGPTL-4 and KIM-1 in the combined form resulted in an area under curve (AUC) of 0.967 (95%CI: 0.932-1.000; p < 0.0001) in the microalbuminuria group and 1 (95%CI: 1.000-1.000; p < 0.0001) in the macroalbuminuria group. The association of urinary levels of ANGPTL-4 and KIM-1 with UACR and eGFR and significant prevalence in the diabetic kidney disease population illustrates the diagnostic potential of these biomarkers.

Correlation of Albuminuria and Diabetic Retinopathy in Type-II Diabetes Mellitus Patients.

BACKGROUND: Diabetic ocular disease is a leading cause of blindness today. The most common microvascular complications of diabetes are diabetic retinopathy and diabetic nephropathy. Multiple risk factors like the duration of the disease, age of the patient, high blood pressure, pregnancy, blood glucose control, and nephropathy have been studied to be associated with the development and progression of diabetic microangiopathy. However, the association of albuminuria has still not been studied in detail, especially in type-II diabetes mellitus. AIM: The primary objective of our study is to quantify the relationship between diabetic retinopathy and urine albumin excretion and to correlate the urinary albumin excretion (normoalbuminuria, microalbuminuria, macroalbuminuria) with the severity and grade (mild, moderate, severe non-proliferative diabetic retinopathy [NPDR] or proliferative diabetic retinopathy [PDR]) of diabetic retinopathy. METHODS: In this cross-sectional study, 250 patients with type-II diabetes above 40 years of age attending the ophthalmic outpatient department (OPD), Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar in India between September 2019 and September 2021 were subjected to a detailed evaluation of history and a thorough ocular examination. Besides, a blood sugar estimation and urine albumin levels were documented. The grade of diabetic retinopathy was correlated with albumin levels. RESULTS: The duration of diagnosis of diabetes ranged from 1-25 years. The association between the grade of diabetic retinopathy and the duration since diagnosis was significant. Sixty-nine percent of the cases were hypertensives, and 66.7% of hypertensives had diabetic retinopathy. In patients without retinopathy, 83.03% had normoalbuminuria levels, and 16.96% had microalbuminuria. In the mild NPDR group, 37.94% of cases had normoalbuminuria, and 62.06% had microalbuminuria. In the moderate NPDR group, 11.1% of cases had normoalbuminuria, and 88.8% had microalbuminuria. In the severe NPDR group, 57.14% of cases had microalbuminuria, while 42.86% had macroalbuminuria. In the very severe NPDR group, 42.86% of cases had microalbuminuria, and 57.14% had macroalbuminuria. In the PDR group, only 6.6% of cases had microalbuminuria, and the rest, 93.3%, had macroalbuminuria. CONCLUSION: This study concluded that there is a definite association between albuminuria and severe diabetic retinopathy in type-II diabetes. Microalbuminuria was a finding associated with all grades of retinopathy with skewing towards the lower grades of diabetic retinopathy; a proportion of diabetics without retinopathy also had microalbuminuria, while macroalbuminuria was associated only with those patients who had either severe NPDR, very severe NPDR, or PDR.

Urinary Albumin to Creatinine Ratio to Predict Diabetic Retinopathy: The Eyes Have It!

Introduction The Coronavirus disease 2019 (COVID-19) pandemic has provided a push in the search for alternative screening methods to replace annual fundoscopic examination of patients with type 2 diabetes mellitus (T2DM) to detect diabetic retinopathy (DR). Materials and methods This retrospective study was conducted using the data of T2DM patients from their routine follow-up hospital visits. The details from their history and physical examination were extracted. As part of their routine follow-up visit, they had undergone a panel of investigations that included blood glucose measurements and urinary albumin excretion measurements. Univariate and logistic multivariate regression analyses were applied to identify the potential clinical and laboratory parameters associated with the presence of DR in them. Results Analysis of the medical records of 272 T2DM patients revealed that 147 patients had DR while 125 did not. Furthermore, 135 had non-proliferative DR (64 mild, 53 moderate, and 18 severe grades), whereas the remaining 12 had proliferative DR. On sequential univariate and multiple regression analysis, urinary albumin creatinine ratio (UACR), known duration of T2DM, and history of ischemic heart disease were seen to be independently associated with the presence of DR. Median UACR for those without DR was 42.6 mg/g (range 18.21-183.3 mg/g) while for those with retinopathy it was 214 mg/g (range 45.4-1260 mg/g) (p<0.001). The receiver operating characteristics curve analysis provided an area under the curve of 70% for UACR. UACR value of 140 mg/g could predict the presence of DR with a sensitivity of 60.5% & specificity of 72%, as well as had positive and negative likelihood ratios of 2.16 and 0.54, respectively. Conclusion UACR has the potential to be used as a screening tool for DR until the easing of social restrictions due to the COVID-19 pandemic.