Early reduction in albuminuria is associated with a steeper 'dip' in initial estimated glomerular filtration rate but favourable long-term kidney outcomes in people with diabetes receiving sodium-glucose cotransporter-2 inhibitors.

AIM: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long-term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors. METHODS: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end-stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. RESULTS: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%-30% decrease, 14.4% (n = 1199) experienced a 0%-30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin-to-creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: -3.6 ± 10.9, -2.0 ± 9.5, -1.1 ± 8.6, and -0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61-4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48-0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. CONCLUSION: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long-term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment.

Association between consumption of flavonol and its subclasses and chronic kidney disease in US adults: an analysis based on National Health and Nutrition Examination Survey data from 2007-2008, 2009-2010, and 2017-2018.

Background: There is little research on the relationship between flavonol consumption and chronic kidney disease (CKD). This study aimed to examine the link between flavonol consumption and the risk of CKD among US adults, using data from the 2007-2008, 2009-2010 and 2017-2018 National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional approach was used, drawing on data from three NHANES cycles. The flavonol consumption of the participants in this study was assessed using a 48 h dietary recall interview. CKD was diagnosed based on an estimated glomerular filtration rate below 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio of 30 mg/g or higher. Results: Compared to the lowest quartile of flavonol intake (Q1), the odds ratios for CKD were 0.598 (95% CI: 0.349, 1.023) for the second quartile (Q2), 0.679 (95% CI: 0.404, 1.142) for the third quartile (Q3), and 0.628 (95% CI: 0.395, 0.998) for the fourth quartile (Q4), with a p value for trend significance of 0.190. In addition, there was a significant trend in CKD risk with isorhamnetin intake, with the odds ratios for CKD decreasing to 0.860 (95% CI: 0.546, 1.354) in the second quartile, 0.778 (95% CI: 0.515, 1.177) in the third quartile, and 0.637 (95% CI: 0.515, 1.177) in the fourth quartile (p for trend = 0.013). Conclusion: Our analysis of the NHANES data spanning 2007-2008, 2009-2010, and 2017-2018 suggests that high consumption of dietary flavonol, especially isorhamnetin, might be linked to a lower risk of CKD in US adults. These findings offer new avenues for exploring strategies for managing CKD.

Transient albuminuria in the setting of short-term severe hyperglycemia in type 1 diabetes.

In a cohort of 1817 children with type 1 diabetes (T1D), short-term hyperglycemia was associated with transient albuminuria (11 % during new-onset T1D without diabetic ketoacidosis (DKA), 12 % during/after DKA, 6 % during routine screening). Our findings have implications regarding future risk of diabetic kidney disease and further investigation is needed.

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

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

Multicenter randomized controlled trial of intensive uric acid lowering therapy for CKD patients with hyperuricemia: TARGET-UA.

BACKGROUND: We investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients. METHODS: This was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment. RESULTS: Three hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups. CONCLUSION: This study did not reveal the benefit of Intensive ULT to improve albuminuria levels. (UMIN000026741 and jRCTs051180146).

Non-steroidal mineralocorticoid antagonists and hyperkalemia monitoring in chronic kidney disease patients associated with type II diabetes: a narrative review.

Chronic kidney disease (CKD) is a prevalent complication of Type II diabetes (T2D). The coexistence of CKD with T2D is comparable to cardiovascular disease (CVD) when the estimated glomerular filtration rate declines below 60 ml/min/1.73 m2. Screening and early detection of people with high risk for CKD would be beneficial in managing CKD progress and the associated complications such as CV complications. Renin-angiotensin-aldosterone system inhibitors (RAASi) have demonstrated beneficial effects in delaying CKD progression, but they carry the risk of hyperkalemia. Nonsteroidal mineralocorticoid antagonists (nsMRA), such as finerenone, exhibit considerable efficacy in their anti-inflammatory, antifibrotic, and renal protective effects with demonstrable reductions in CV complications. In addition, nsMRAs do not cause significant changes in serum potassium levels compared to traditional steroidal MRA. Ongoing research explores the capacity of the sodium-glucose transport protein 2 inhibitors (SGLT-2i), combined with nsMRA, to produce synergistic renal protective effects and reduce the risk of hyperkalemia. Also, a dedicated renal outcomes study (FLOW study) involving a once-weekly injectable Glucagon-like peptide-1 receptor agonist, semaglutide, was halted early by the data monitoring committee due to having achieved the predefined efficacy endpoint and considerations related to renal disease. In CKD patients with T2D on nsMRA, hyperkalemia management requires a comprehensive approach involving lifestyle adjustments, dietary modifications, regular serum potassium level monitoring, and potassium binders, if necessary. Withholding or down-titration of nsMRAs with close monitoring of serum potassium levels may be required in patients with concerning potassium levels. In light of the current state of knowledge, this review article explores the perspectives and approaches that HCPs may consider when monitoring and managing hyperkalemia in CKD patients with T2D.

Chronic Kidney Disease (CKD) is a common and serious problem among people with Type II Diabetes (T2D). People who have CKD with T2D are at a higher risk for heart disease after normal kidney function declines below certain levels. Renin-angiotensin-aldosterone system inhibitors are a group of medications that can help delay CKD progression but may cause a rise in circulating potassium levels. Nonsteroidal mineralocorticoid antagonist (nsMRA), such as finerenone, can reduce kidney inflammation and damage, with noted cardiovascular benefits, and with less effect on serum potassium levels as compared to their steroid-based counterparts. Researchers are studying whether combining blood sugar medications such as sodium-glucose transport protein-2 inhibitors (SGLT-2i) and finerenone can help protect the kidneys and heart. They also want to see if this combination can prevent high potassium levels. This article talks about ways to check and monitor potassium levels in CKD patients with T2D who may be taking nsMRA. To manage high potassium levels in people with CKD and T2D, doctors may suggest lifestyle changes, dietary adjustments, potassium-lowering medication, or adjustment of other medications with close monitoring of potassium levels.

An elevated urinary albumin-to-creatinine ratio increases the risk of incident cardia-cerebrovascular disease in individuals with type 2 diabetes.

AIMS: We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2 diabetes(T2D). METHODS: We included 8975 participants with T2D but free of prevalent CVD (including myocardial infarction, ischemic and hemorrhagic stroke) at baseline from Kailuan study who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3-30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). Cox regression models and restricted cubic spline were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance. RESULTS: During a median follow-up of 4.05 years, 560 participants developed first CVD event (6.24%). After adjustment for potential confounders, participants with microalbuminuria had higher risks of CVD compared with normal uACR, with HRs of 1.57(95% CI 1.04-2.37) for myocardial infarction, 1.24(95% CI 1.00-1.54) for ischemic stroke,1.62(95% CI 0.73-3.61) for hemorrhagic stroke, and 1.30(95% CI 1.07-1.57) for total CVD. The risks gradually attenuated with uACR increase, with HRs of 2.86(95% CI 1.63-5.00) for myocardial infarction, 2.46(95% CI 1.83-3.30) for ischemic stroke, 4.69(95% CI 1.72-12.78) for hemorrhagic stroke, and 2.42(95% CI 1.85-3.15) for total CVD in macroalbuminuria. The addition of uACR to established CVD risk models improved the CVD risk prediction efficacy. CONCLUSIONS: Increasing uACR, even below the normal range, is an independent risk factor for new-onset CVD in T2D population. Furthermore, uACR could improve the risk prediction for CVD among community based T2D patients.

Kidney and liver fat accumulation: from imaging to clinical consequences.

BACKGROUND: Recent studies indicate that accumulation of adipose tissue in various organs such as liver and kidney may contribute to the pathophysiology of metabolic syndrome. We aim to investigate the association between kidney and liver adipose tissue accumulation, assessed by the magnetic resonance imaging (MRI) proton density fat fraction technique, along with its relation to clinical and biochemical parameters. METHODS: We included 51 volunteers with phenotypical features of metabolic syndrome (mean age = 34 years, mean body-mass index = 26.4 kg/m2) in our study in which liver and kidney adipose tissue accumulation was assessed via MRI-proton density fat fraction along with multiple other clinical and biochemical parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio, serum lipid profile, liver function tests and body-mass index (BMI). RESULTS: Our results from the univariate linear regression analysis indicate that both the kidney and liver scores were positively correlated with markers such as BMI, urine albumin-to-creatinine ratio, triglycerides (p < 0.001) and negatively correlated with eGFR (p < 0.05). In multivariate analysis, urine albumin-to-creatinine ratio (p < 0.05), triglycerides (p < 0.01), eGFR (p < 0.05) and BMI (p < 0.001) were found to be independently associated with kidney and liver fat accumulation, respectively (R2 = 0.64; R2 = 0.89). There was also a positive correlation between kidney and liver fat accumulation. CONCLUSION: We have found a significant association between adipose tissue accumulation in liver and kidney and the parameters of metabolic syndrome. Moreover, the presence of a strong association between kidney and liver fat accumulation and kidney function parameters such as urine albumin-to-creatinine ratio and eGFR may be an indicator of the clinical significance of parenchymal fat accumulation.

Mid-Trimester Spot Urinary Albumin/Creatinine Ratio as a Screening Tool in Prediction of Pre-eclampsia.

Aims and Objectives: To determine utilization of spot urinary albumin/creatinine ratio (UACR) to predict subsequent development of preeclampsia, measured between 17 and 24 weeks of gestational age in asymptomatic antenatal woman and determine their maternal and neonatal outcomes. Introduction: In preeclampsia the basic pathology is generalized endothelial dysfunction. It causes glomerular endotheliosis which leads to proteinuria, decreased glomerular filtration rate and renal blood flow. Thus microalbuminuria is an early marker which can measured to predict preeclampsia. Materials and Methods: It is a prospective observational study, carried out for one year in a cohort of asymptomatic antenatal women at 17-24 weeks of gestational age, attending hospital for routine antenatal check-up with a singleton pregnancy and no associated complications. Urine albumin and creatinine ratio (UACR) is measured at first visit, and women were followed till delivery and the maternal and foetal outcomes were recorded. Results: Out of 81 pregnant women enrolled in the study, 58% belonged to 18-25 years, 54.3% belonged to lower middle class. There was a significant difference in mean UACR among women who developed preeclampsia (PE) and gestational diabetes mellitus (GDM) with p value < 0.05. In the study there was significant association between severe PE, PE and GDM with UACR at 22 as cut-off, with p value < 0.05. In the study among those with UACR > 22, 2.5% had IUFD, 12.5% had LBW, and 7.5% were admitted to NICU. Conclusion: With the measurement of spot UACR in mid-trimester we can predict the development of preeclampsia before the onset of clinical manifestations. UACR > = 171 mg/g predicted preeclampsia well before the onset of clinical manifestations with high sensitivity of 83.3% and specificity of 98.6%. Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-023-01862-9.

[Kidney diseases in type 2 diabetes mellitus : Overview and implementation of guidelines, position papers and practical recommendations for diagnostics and monitoring]. / Nierenerkrankungen bei Diabetes mellitus Typ 2 : Überblick und Implementierung der Leitlinien, Positionspapiere und Praxisempfehlungen zur Diagnostik und Überwachung.

BACKGROUND: National and international medical societies have published guidelines and recommendations pertaining to the diagnostics and monitoring of chronic kidney disease in patients with type 2 diabetes mellitus. Consistency and implementation in daily clinical practice are rarely reported. OBJECTIVE: This article provides an overview on recommendations as a reflection of the global state of the art and assesses the implementation in daily practice in Germany, which was collected via a representative questionnaire. MATERIAL AND METHODS: The current guidelines were compared with respect to the consistency of parameters, frequency of testing and recommendations for nephrological referrals. The results were then compared with the survey responses to estimate the level of their implementation in daily practice in Germany. RESULTS: According to the recommendations the estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (UACR) should be tested at least once per year in all patients with type 2 diabetes. In cases of more severe kidney impairment (above Kidney Disease:Improving Global Outcomes, KDIGO, stage 3b with eGFR < 45 ml/min/1,73 m2) or albuminuria (from stage A2), more frequent measurements and nephrological referrals are recommended; however, different threshold values and frequencies are recommended. The responses from the questionnaires indicate that eGFR is tested annually in 96.5% of all cases and albuminuria is tested in 77.2% of cases. An eGRF triggered referral to a nephrologist is implemented by 19.6% of all nonnephrological practitioners, albuminuria triggered referrals are implemented in the majority of cases. CONCLUSION: Measurement of eGFR is the established standard in Germany. Potential improvement was found in albumin measurement, the frequency of testing and the time point for nephrological consultation. All guidelines emphasize the benefits of interdisciplinary cooperation.

Early diagnosis of chronic kidney disease in patients with diabetes in France: multidisciplinary expert opinion, prevention value and practical recommendations.

Diabetes is the leading cause of end-stage kidney disease (ESKD), accounting for approximately 50% of patients starting dialysis. However, the management of these patients at the stage of chronic kidney disease (CKD) remains poor, with fragmented care pathways among healthcare professionals (HCPs). Diagnosis of CKD and most of its complications is based on laboratory evidence. This article provides an overview of critical laboratory evidence of CKD and their limitations, such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), Kidney Failure Risk Equation (KFRE), and serum potassium. eGFR is estimated using the CKD-EPI 2009 formula, more relevant in Europe, from the calibrated dosage of plasma creatinine. The estimation formula and the diagnostic thresholds have been the subject of recent controversies. Recent guidelines emphasized the combined equation using both creatinine and cystatin for improved estimation of GFR. UACR on a spot urine sample is a simple method that replaces the collection of 24-hour urine. Albuminuria is the preferred test because of increased sensitivity but proteinuria may be appropriate in some settings as an alternative or in addition to albuminuria testing. KFRE is a new tool to estimate the risk of progression to ESKD. This score is now well validated and may improve the nephrology referral strategy. Plasma or serum potassium is an important parameter to monitor in patients with CKD, especially those on renin-angiotensin-aldosterone system (RAAS) inhibitors or diuretics. Pre-analytical conditions are essential to exclude factitious hyperkalemia. The current concept is to correct hyperkalemia using pharmacological approaches, resins or diuretics to be able to maintain RAAS blockers at the recommended dose and discontinue them at last resort. This paper also suggests expert recommendations to optimize the healthcare pathway and the roles and interactions of the HCPs involved in managing CKD in patients with diabetes.

Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis.

BACKGROUND: Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. METHODS: Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45-<60 versus ≥ 60 mL/min/1.73 m2) or damage (urine albumin:creatinine ratio [UACR] ≥ 30-≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA1c), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated. RESULTS: Independently of treatment, participants with reduced kidney function (eGFR ≥ 45-<60 and < 45 mL/min/1.73 m2: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30-≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] > 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT>0.05); reductions in BW were affected by baseline eGFR (pINT<0.001) but not UACR (pINT>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. CONCLUSIONS: MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. TRIAL REGISTRATIONS: NCT01720446; NCT02692716.

Elevated urine albumin creatinine ratio increases cardiovascular mortality in coronary artery disease patients with or without type 2 diabetes mellitus: a multicenter retrospective study.

BACKGROUND: Albuminuria has been suggested as an atherosclerotic risk factor among the general population. However, whether this association will be amplified in patients with coronary artery disease (CAD) is unknown. It is also unknown whether diabetes mellitus confounds the association. We aim to analyse the prognosis of elevated urine albumin creatinine ratio (uACR) in the CAD population with or without type 2 diabetes mellitus (T2DM). METHODS: This multi-center registry cohort study included 5,960 patients with CAD. Patients were divided into T2DM and non-T2DM group, and baseline uACR levels were assessed on three grades (low: uACR < 10 mg/g, middle: 10 mg/g ≤ uACR < 30 mg/g, and high: uACR ≥ 30 mg/g). The study endpoints were cardiovascular mortality and all-cause mortality. RESULTS: During the median follow-up of 2.2 [1.2-3.1] years, 310 (5.2%) patients died, of which 236 (4.0%) patients died of cardiovascular disease. CAD patients with elevated uACR had a higher risk of cardiovascular mortality (middle: HR, 2.32; high: HR, 3.22) than those with low uACR, as well as all-cause mortality. Elevated uACR increased nearly 1.5-fold risk of cardiovascular mortality (middle: HR, 2.33; high: HR, 2.34) among patients without T2DM, and increased 1.5- fold to 3- fold risk of cardiovascular mortality in T2DM patients (middle: HR, 2.49; high: HR, 3.98). CONCLUSIONS: Even mildly increased uACR could increase the risk of cardiovascular mortality in patients with CAD, especially when combined with T2DM.

Estimated health economic impact of conducting urine albumin-to-creatinine ratio testing alongside estimated glomerular filtration rate testing in the early stages of chronic kidney disease in patients with type 2 diabetes.

AIM: To estimate the health economic impact of undertaking urine albumin-to-creatinine ratio (UACR) testing versus no UACR testing in early stages of chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D). METHODS: An economic model, taking a UK healthcare system perspective, estimated the impact of UACR testing on additional costs, clinical benefits measured as prevented dialyses and cardiovascular-related deaths, life years gained (LYg), LYg before kidney failure, and incremental cost-effectiveness ratio (ICER). Sixteen of the 18 Kidney Disease: Improving Global Outcomes (KDIGO) heatmap categories were considered separately, and grouped in health states according to CKD risk. Results were derived for current standard-of-care and emerging CKD therapies. RESULTS: The cohort that adhered to both UACR and estimated glomerular filtration rate (eGFR) testing guidelines in early stages of CKD (n = 1000) was associated with approximately 500 LYg before kidney failure onset; costing approximately £2.5 M. ICERs across the KDIGO heatmap categories were approximately £5,000. LIMITATIONS: This model used data from a comprehensive meta-analysis that was initiated more than 10 years ago (2009). While this was the most comprehensive source identified, recent changes in the treatment landscape, patient population and social determinants of CKD will not be captured. Furthermore, a narrow approach was taken, aligning included costs with UK NHS reference materials. This means that some direct and indirect drivers of costs in late-stage disease have been excluded. CONCLUSIONS: UACR testing in the early stages of CKD is cost effective in T2D patients. Emerging therapies with the potential to slow CKD progression, mean that optimal monitoring through UACR/eGFR testing will become increasingly important for accurate identification and timely treatment initiation, particularly for the highest-risk A3 category.

Accuracy of Spot Urine Albumin Creatinine Ratio With Respect to 24-Hour Urine Albumin for the Detection of Proteinuria in Antenatal Women With Preeclampsia: A Descriptive Study.

Background Among the hypertensive disorders of pregnancy, certain diseases like preeclampsia (PE) and eclampsia have the maximum impact on morbidity and mortality of the mother as well as the newborn. Proteinuria determination is used to assess renal damage in PE. There are several ways to evaluate proteinuria in pregnant women, but the gold standard remains the 24-hour urine albumin (24-h UA) excretion. Spot urine albumin creatinine ratio (UACR) can be used for rapid diagnosis of PE which is fast, reliable, and easy to use. Hence, our tertiary care center conducted the current study to assess the accuracy of spot UACR with 24-h UA for detecting proteinuria in antenatal women to diagnose PE and to evaluate the obstetric outcome in antenatal women with PE. Methodology A descriptive, cross-sectional study was conducted on 98 antenatal women diagnosed with PE. Urine albumin was done by dipstick method and the presence or absence of proteinuria was noted. Both, the 24-h urine sample and a random sample for spot UACR were sent for analysis. Results Spot UACR has more specificity than sensitivity along with a high negative predictive value for the detection of proteinuria. Additionally, significant proteinuria was associated with an increased rate of induced labor, a cesarean section in patients, lower mean gestational age at the time of delivery, lower birth weight, and increased rate of intrauterine fetal death. Conclusion The study concluded that spot UACR has more specificity than sensitivity along with a high negative predictive value for the detection of proteinuria and therefore, can be used for the diagnosis of proteinuria in women with PE. Hence, spot UACR is a reliable, faster, and more accurate method for the detection of proteinuria in PE and can be used for early diagnosis and timely management leading to a decrease in mortality and morbidity of the mother and the fetus.

[Key guidelines on the Spanish multi-society consensus on chronic kidney disease]. / Consideraciones sobre el consenso español multisociedad de manejo de la enfermedad renal crónica.

Chronic kidney disease (CKD) is a global health problem and affects approximately 15.1% of the general population in Spain (IBERICAN and ENRCA studies), although most of the literature agrees that there is an underdiagnosis that would further increase this prevalence. This article from the CKD monograph aims to summarize the main consensus guidelines for the management of CKD, highlighting the most important and novel aspects, as well as recently updated terminology and concepts. Sections addressing specific populations and prevention strategies are also included. As the family doctor (MAP) plays a fundamental role in the detection of CKD, recommendations on the multidisciplinary approach to CKD are collected.

Prediction of CKD Progression and Cardiovascular Events Using Albuminuria and Pulse Wave Velocity.

INTRODUCTION: Chronic kidney disease (CKD) is associated with cardiovascular disease (CVD) and death. Albuminuria is an established risk factor, but additional biomarkers predicting CKD progression or CVD are needed. Arterial stiffness is an easily measurable parameter that has been associated with CVD and mortality. We evaluated the ability of carotid-femoral pulse wave velocity (PWV) and urine albumin-creatinine (UAC) ratio to predict CKD progression, cardiovascular events, and mortality in a cohort of CKD patients. METHODS: In CKD stage 3-5 patients, PWV and UAC were measured at baseline. CKD progression was defined as 50% decline in estimated glomerular filtration rate (eGFR), initiation of dialysis, or renal transplantation. A composite endpoint was defined as CKD progression, myocardial infarction, stroke, or death. Endpoints were analyzed using Cox regression analysis adjusted for possible confounders. RESULTS: We included 181 patients (median age 69 [interquartile range 60-75] years, 67% males) with a mean eGFR of 37 ± 12 mL/min/1.73 m2 and UAC 52 (5-472) mg/g. Mean PWV was 10.6 m/s. Median follow-up until first event was 4 (3-6) years with 44 and 89 patients reaching a CKD progression or composite endpoint, respectively. UAC (g/g) significantly predicted both CKD progression (HR 1.5 [1.2; 1.8]) and composite endpoints (HR 1.4 [1.1; 1.7]) in adjusted Cox regression. In contrast, PWV (m/s) was not associated with neither CKD progression (HR 0.99 [0.84; 1.18]) nor the composite endpoint (HR 1.03 [0.92; 1.15]). CONCLUSION: In an aging CKD population, UAC predicted both CKD progression and a composite endpoint of CKD progression, cardiovascular events, or death, while PWV did not.

Efficacy and safety of sodium glucose cotransporter 2 inhibitors plus standard care in diabetic kidney disease: A systematic review and meta-analysis.

INTRODUCTION: Many people with type 2 diabetes progress to end-stage diabetic kidney disease (DKD) despite blockade of the renin-angiotensin system, suggesting the need for innovative treatment options for DKD. To capture the findings of recent studies, we performed an updated systematic review and meta-analysis of the efficacy and safety of sodium glucose co-transporter 2 (SGLT2) inhibitors combined with standard care involving angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) on the development and progression of DKD in people with type 2 diabetes compared with standard care alone. METHODS: The Cochrane Library, MEDLINE, EMBASE, PubMed and clinical trials registers were systematically searched for randomized controlled trials published before 1 September 2022. Primary outcomes were urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Secondary outcomes were glycated hemoglobin (HbA1c) and systolic blood pressure (SBP). Relative risk was calculated for adverse events. RESULTS: Eight studies enrolling 5512 participants were included. In the meta-analysis (n = 1327), SGLT2 inhibitors were associated with a statistically significant reduction in UACR (weighted mean difference [WMD] -105.61 mg/g, 95 % CI -197.25 to -13.98, I2 = 99 %, p = 0.02). There was no statistically significant difference in relation to eGFR (n = 1375; WMD -0.23 mL/min/1.73m2, 95 % CI -4.34 to 3.89, I2 = 94 %, p = 0.91). CONCLUSIONS: SGLT2 inhibitors in addition to standard care including ACE inhibitors and/or ARBs significantly reduced albuminuria, HbA1c and SBP when compared to standard care alone, supporting their routine use in people with type 2 diabetes.

Increased serum PCSK9 levels are associated with renal function impairment in patients with type 2 diabetes mellitus.

PURPOSE: The purpose of this study was to investigate the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and renal function impairment in type 2 diabetes mellitus (T2DM) patients. METHODS: PCSK9 levels were measured in T2DM patients, streptozotocin plus high-fat diet (STZ + HFD) mice, human proximal tubular epithelial (HK-2) cells treated with high glucose plus palmitic acid (HGPA) and the corresponding control groups. The T2DM patients were further divided into three groups according to serum PCSK9 levels. An analysis of clinical data was conducted, and a binary logistic regression model was used to test the relationship between potential predictors and urine albumin/urine creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). RESULTS: PCSK9 levels were higher in the DM group than in the control group in humans, mice and HK-2 cells. The systolic blood pressure (SBP), serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), and urine α1-MG/urine creatinine ratio (UαCR) values in PCSK9 tertile 3 were significantly higher than those in PCSK9 tertile 1 (p < 0.05). The DBP and UACR values were significantly higher in PCSK9 tertile 3 than in PCSK9 tertile 1 and PCSK9 tertile 2 (both p < 0.05). In addition, URCR values were significantly higher in PCSK9 tertile 3 and PCSK9 tertile 2 than in PCSK9 tertile 1 (both p < 0.05). Serum PCSK9 levels were positively correlated with SBP, Scr, BUN, TG, URCR, UαCR and UACR but inversely correlated with eGFR. In STZ + HFD mice, serum PCSK9 levels were positively correlated with Scr, BUN and UACR, which was consistent with the findings in the patients. A logistic regression model revealed that serum PCSK9 is an independent risk factor for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m2. The ROC curve showed that 170.53 ng/mL and 337.26 ng/mL PCSK9 were the best cutoff values for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m2, respectively. CONCLUSION: Serum PCSK9 levels are associated with renal function impairment in T2DM patients and in some patients lower PCSK9 may be helpful to decrease chronic kidney disease.

Retinal microvascular changes in diabetic patients with diabetic nephropathy.

BACKGROUND: To explore the characteristics of retina microvascular changes in patients with diabetic nephropathy (DN) and its risk factors. METHODS: Retrospective, observational study. 145 patients with type 2 diabetic mellitus (DM) and DN were included in the study. Demographic and clinical parameters were obtained from medical records. Presence of diabetic retinopathy (DR), hard exudates (HEs) and diabetic macular edema (DME) were evaluated according to the color fundus images, optical coherence tomography (OCT) and fluorescence angiography (FFA). RESULTS: DR accounted for 61.4% in type 2 DM patients with DN, of which proliferative diabetic retinopathy (PDR) accounted for 23.6% and sight threatening DR accounted for 35.7%. DR group had significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004), HbA1c (P = 0.037), Urine albumin creatine ratio (ACR) (p < 0.001) and lower level of estimated glomerular filtration rate (eGFR) (P = 0.013). Logistic regression analysis showed DR was significantly associated with ACR stage (p = 0.011). Subjects with ACR stage3 had higher incidence of DR compared with subjects with ACR stage1 (OR = 24.15, 95%CI: 2.06-282.95). 138 eyes of 138 patients were analyzed for HEs and DME, of which 23.2% had HEs in posterior pole and 9.4% had DME. Visual acuity was worse in HEs group than in non-HEs group. There was significant difference in the LDL-C cholesterol level, total cholesterol (CHOL) level and ACR between HEs group and non-HEs group. CONCLUSIONS: A relatively higher prevalence of DR was found in type 2 DM patients with DN. ACR stage could be recognized as a risk factor for DR in DN patients. Patients with DN needs ophthalmic examination more timely and more frequently.