Risk factors for lower renal compensation after nephrectomy: an analysis of living kidney donors in an Amazonian cohort / Fatores de risco para menor compensação renal pós-nefrectomia: análise de doadores de rim vivo em uma coorte amazônica

Abstract Introduction: Living donor kidney transplantation is considered the ideal renal replacement therapy because it has a lower complication rate and allows an efficient response to the high demand for grafts in the healthcare system. Careful selection and adequate monitoring of donors is a key element in transplantation. Individuals at greater risk of developing kidney dysfunction after nephrectomy must be identified. Objective: To identify risk factors associated with a renal compensation rate (CR) below 70% 12 months after nephrectomy. Methods: This observational retrospective longitudinal study included living kidney donors followed up at the Lower Amazon Regional Hospital between 2016 and 2022. Data related to sociodemographic variables, comorbid conditions and kidney function parameters were collected. Results: The study enrolled 32 patients. Fourteen (43.75%) had a CR < 70% 12 months after kidney donation. Logistic regression found obesity (Odds Ratio [95%CI]: 10.6 [1.7-65.2]), albuminuria (Odds Ratio [95%CI]: 2.41 [1.2-4.84]) and proteinuria (Odds Ratio [95%CI]: 1.14 [1.03-1.25]) as risk factors. Glomerular filtration rate was a protective factor (Odds Ratio [95% CI]: 0.92 [0.85-0.99]). Conclusion: Obesity, albuminuria and proteinuria adversely affected short-term renal compensation rate. Further studies are needed to uncover the prognostic implications tied to these risk factors. Our findings also supported the need for careful individualized assessment of potential donors and closer monitoring of individuals at higher risk.

Resumo Introdução: O transplante de rim de doador vivo é considerado a terapia renal substitutiva ideal por oferecer menor taxa de complicações e possibilitar uma resposta eficiente à grande demanda por enxertos no sistema de saúde. A seleção criteriosa e o acompanhamento adequado dos doadores constituem um pilar fundamental dessa modalidade terapêutica, sendo essencial a identificação dos indivíduos em maior risco de disfunção renal pós-nefrectomia. Objetivo: Identificar fatores de risco para uma Taxa de Compensação (TC) da função renal inferior a 70% 12 meses após a nefrectomia. Métodos: Estudo observacional, retrospectivo e longitudinal conduzido com doadores de rim vivo acompanhados no Hospital Regional do Baixo Amazonas entre 2016 e 2022. Foram coletados dados correspondentes a variáveis sociodemográficas, comorbidades e parâmetros de função renal. Resultados: Foram incluídos 32 pacientes na amostra final. Destes, 14 (43,75%) obtiveram TC < 70% 12 meses após a doação. A regressão logística identificou a obesidade (Odds Ratio [IC95%]: 10.6 [1.7-65.2]), albuminúria (Odds Ratio [IC95%]: 2.41 [1.2-4.84]) e proteinúria (Odds Ratio [IC95%]: 1.14 [1.03-1.25]) como fatores de risco. A taxa de filtração glomerular atuou como fator de proteção (Odds Ratio [IC95%]: 0.92 [0.85-0.99]). Conclusão: Obesidade, albuminúria e proteinúria demonstraram impacto negativo na taxa de compensação renal em curto prazo, o que reitera a necessidade de estudos acerca das implicações prognósticas desses fatores. Além disso, reforça-se a necessidade de avaliação cuidadosa e individualizada dos possíveis doadores, com acompanhamento rigoroso, especialmente para indivíduos de maior risco.

Accuracy of glomerular filtration rate estimation using creatinine and cystatin C for identifying and monitoring moderate chronic kidney disease: the eGFR-C study.

Background: Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS. Objectives: Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies. Design: A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline (n = 1167) and their ability to detect change over 3 years (n = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components (n = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs (n = 875). Setting: Primary, secondary and tertiary care. Participants: Adults (≥ 18 years) with stage 3 chronic kidney disease. Interventions: Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Main outcome measures: Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated. Results: Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine-cystatin equation (94.9%) was superior (p < 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 years = £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/-17.7, with lower reference change values for estimated glomerular filtration rate. Limitations: Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target. Future work: Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken. Conclusions: Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease. Trial registration: This trial is registered as ISRCTN42955626. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

Chronic kidney disease, which affects approximately 14% of the adult population, often has no symptoms but, in some people, may later develop into kidney failure. Kidney disease is most often detected using a blood test called creatinine. Creatinine does not identify everyone with kidney disease, or those most likely to develop more serious kidney disease. An alternative blood test called cystatin C may be more accurate, but it is more expensive than the creatinine test. We compared the accuracy of these two tests in more than 1000 people with moderate kidney disease. Participants were tested over 3 years to see if the tests differed in their ability to detect worsening kidney function. We also wanted to identify risk factors associated with loss of kidney function, and how much the tests normally vary to better understand what results mean. We compared the accuracy and costs of monitoring people with the two markers. Cystatin C was found slightly more accurate than the creatinine test at estimating kidney function when comparing the baseline single measurements (95% accurate compared to 90%), but not at detecting worsening function over time. This means that the additional cost of monitoring people over time with cystatin C to detect kidney disease progression could not be justified. Kidney test results could vary by up to 20% between tests without necessarily implying changes in underlying kidney function ­ this is the normal level of individual variation. Cystatin C marginally improved accuracy of kidney function testing but not ability to detect worsening kidney function. Cystatin C improves identification of moderate chronic kidney disease, but our results do not support its use for routine monitoring of kidney function in such patients.

Long-term comparison of renal and metabolic outcomes after sodium-glucose co-transporter 2 inhibitor or glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes.

BACKGROUND: Renal outcomes in patients with type 2 diabetes following treatment with sodium-glucose co-transporter-2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP1RAs) have not been directly compared. This study compared the impact of SGLT2i and GLP1RA therapy on renal function and metabolic parameters. METHODS: Patients with type 2 diabetes who initiated SGLT2i or GLP1RA therapy in a tertiary hospital between January 2009 and August 2023 were included to assess composite renal outcomes, such as a 40% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease, renal death, or new-onset macroalbuminuria. Alterations in blood pressure, glucose regulation parameters, lipid profile, and anthropometric parameters, including body fat and muscle masses, were examined over 4-years. RESULTS: A total of 2,112 patients were enrolled using a one-to-three propensity-score matching approach (528 patients for GLP1RAs, 1,584 patients for SGLT2i). SGLT2i treatment was favoured over GLP1RA treatment, though not significantly, for composite renal outcomes (hazard ratio [HR], 0.63; p = 0.097). SGLT2i therapy preserved renal function effectively than GLP1RAs (decrease in eGFR, ≥ 40%; HR, 0.46; p = 0.023), with improving albuminuria regression (HR, 1.72; p = 0.036). SGLT2i therapy decreased blood pressure and body weight to a greater extent. However, more patients attained HbA1c levels < 7.0% with GLP1RAs than with SGLT2is (40.6% vs 31.4%; p < 0.001). GLP1RA therapy enhanced ß-cell function and decreased LDL-cholesterol levels below baseline values. CONCLUSIONS: SGLT2is were superior for preserving renal function and reducing body weight, whereas GLP1RAs were better for managing glucose dysregulation and dyslipidaemia.

Associations of Insulin Resistance and High-Sensitivity C-Reactive Protein with Metabolic Abnormalities in Korean Patients with Type 2 Diabetes Mellitus: A Preliminary Study.

We conducted this single-center, retrospective, cohort study to examine whether insulin resistance (IR) and high-sensitivity C-reactive protein (hsCRP) have a relationship with metabolic abnormalities in patients with type 2 diabetes mellitus (T2DM). In a total of 3758 patients (n = 3758) with T2DM, we analyzed medical records and thereby evaluated their baseline characteristics such as age, sex, duration of T2DM, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference, body mass index (BMI), visceral fat thickness (VFT), fasting plasma insulin levels, C-peptide levels, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of ß-cell function (HOMA-ß), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), albuminuria, intima-media thickness (IMT) and hsCRP. The patients were stratified according to the tertile of the K index of the insulin tolerance test (KITT) or hsCRP. Thus, they were divided into the lowest (≥2.37), middle (1.54-2.36) and highest tertile (0-1.53) of KITT and the lowest (0.00-0.49), middle (0.50-1.21) and highest tertile (≥1.22) of hsCRP. Moreover, associations of KITT and hsCRP with metabolic abnormalities, such as steatotic liver disease (SLD), metabolic syndrome (MetS), albuminuria, diabetic retinopathy and carotid atherosclerosis, were also analyzed. There was a significant positive correlation between the prevalence of SLD, MetS, albuminuria and diabetic retinopathy and KITT (p < 0.001). Moreover, there was a significant positive association between the prevalence of SLD, MetS and albuminuria and hsCRP (p < 0.001). In conclusion, our results indicate that clinicians should consider the relationships of IR and hsCRP with metabolic abnormalities in the management of patients with T2DM. However, further large-scale, prospective, multi-center studies are warranted to confirm our results.

Cardiovascular and Kidney Outcomes of Non-Diabetic CKD by Albuminuria Severity: Findings From the CRIC Study.

RATIONALE & OBJECTIVE: The clinical trajectory of normoalbuminuric chronic kidney disease (CKD), particularly in the absence of diabetes, has not yet been well-studied. This study evaluated the association of kidney and cardiovascular outcomes with levels of albuminuria in a cohort of patients with non-diabetic CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,463 adults with non-diabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Albuminuria stage at study entry. OUTCOME: Primary outcome: Composite kidney (halving of eGFR, kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death. ANALYTICAL APPROACH: Linear mixed effects and Cox proportional hazards regression analyses. RESULTS: Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [aHR] 3.3, 95% CI 2.4-4.6; aHR 8.6, 95% CI 6.0-12.0) and cardiovascular outcomes (aHR 1.5, 95% CI 1.2-1.9; aHR 1.5, 95% CI 1.1-2.0). Those with normoalbuminuria (<30 mcg/mg; N=863) had a slower decline in eGFR (-0.46 mL/min/1.73m2/year), compared to those with moderate (30-300 mcg/mg, N=372; 1.41 mL/min/1.73m2/ year), or severe albuminuria (>300 mcg/mg, N=274; 2.63 mL/min/1.73m2/year). Kidney outcomes, in adjusted analyses, occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared to those with normoalbuminuria (9.3 years), whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively). LIMITATIONS: Self-report of CKD etiology without confirmatory kidney biopsies. Residual confounding. CONCLUSIONS: Participants with normoalbuminuric non-diabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria.

Chronic Kidney Disease Stage and Cardiovascular and Mortality Events Among Older Adults: The SPRINT Trial.

Rationale & Objective: The risk implications of the Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease classification in older adults are controversial. We evaluated the risk of adverse outcomes in this population across categories of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Study Design: Prospective cohort. Settings & Participants: In total, 2,509 participants aged ≥75 years in the Systolic Blood Pressure Intervention Trial (SPRINT). Exposure: KDIGO eGFR and UACR categories. We combined KDIGO categories G1 and G2, G3b and G4, as well as A2 and A3. Outcomes: Primary SPRINT outcome (composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), and all-cause death. Analytical Approach: Multivariable Cox proportional hazard models. Results: Mean age was 79.8 years, and 37.4% were female. The mean eGFR was 64.0 mL/min/1.73 m2, and the median UACR was 13.1 mg/g. In multivariable Cox proportional hazard analysis, compared with participants with eGFR ≥ 60 mL/min/1.73 m2 and UACR < 30 mg/g, there was no statistically significant difference in the risk of the primary outcome among participants with eGFR 45-59 or 15-44 mL/min/1.73 m2 and UACR < 30 mg/g. However, those with eGFR 45-59 or 15-44 mL/min/1.73 m2 and UACR ≥ 30 mg/g had higher risk of the primary outcome (HR [95% CI], 1.97 [1.27-3.04] and 3.32 [2.23-4.93], respectively). The risk for all-cause death was higher for each category of abnormal eGFR and UACR, with the highest risk observed among those with eGFR 15-44 mL/min/1.73 m2 and UACR ≥ 30 mg/g (3.34 [2.05-5.44]). Limitations: Individuals with diabetes and urine protein >1 g/day were excluded from SPRINT. Conclusion: Among older adults SPRINT participants, low eGFR without albuminuria was associated with higher mortality but not with increased risk of cardiovascular events. Additional studies are needed to evaluate an adapted chronic kidney disease stage-based risk stratification for older adults.

Using data from participants in the SPRINT trial, we evaluated the association of chronic kidney disease stage with adverse clinical outcomes among adults older than 75 years without diabetes. We found that low level of kidney function determined by a low estimated glomerular filtration rate with moderately or severely increased urine albumin excretion was associated with increased risk for cardiovascular events and all-cause mortality. However, low estimated glomerular filtration rate with normal or mildly increased urinary albumin excretion was not consistently associated with these adverse outcomes. This finding supports the need for additional studies to evaluate an age-adapted classification of chronic kidney disease to improve risk stratification among older adults.

Guidelines for clinical evaluation of chronic kidney disease in early stages : AMED research on regulatory science of pharmaceuticals and medical devices.

BACKGROUND: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients. METHODS: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal. RESULTS: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review. CONCLUSION: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors.

Real-Life Experience on the Effect of SGLT2 Inhibitors vs. Finerenone vs. Combination on Albuminuria in Chronic Kidney Disease.

BACKGROUND: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting. METHODS: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m2 and a urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were included. Patients were divided into three groups: two monotherapy groups of SGLT2 inhibitors or finerenone and a third combination group of therapy with SGLT2 inhibitors for the first 4 months and SGLT2 inhibitors and finerenone subsequently. The primary outcomes were the timing and percentage of patients achieving a >50% reduction in UACR from baseline. RESULTS: Group 1 comprised 52 patients on SGLT2i, group 2 had 22 patients on finerenone, and group 3 had 24 patients on combination therapy. The baseline median UACR and mean eGFR were 513 mg/g and 47.9 mL/min per 1.73 m2 in group 1, 548.0 mg/g and 50.5 mL/min per 1.73 m2 in group 2, and 800 mg/g and 60 mL/min per 1.73 m2 in group 3. At baseline, 71 (72.4%) patients were on the angiotensin-converting enzyme inhibitor (ACEi) or the angiotensin receptor blocker (ARB), and 78 (79.5%) patients had type 2 diabetes. After 8 months of follow-up, a >50% decrease in albuminuria was achieved in 96% of patients in group 3, compared to 50% in group 1 and 59% in group 2 (p-values were <0.01 and <0.01, respectively). There was a statistically but not clinically significant change in mean potassium levels in group 2 (+0.4 mmol/L) compared to either group 1 (0.0 mmol/L with p-value: <0.01) or group 3 (-0.01 mmol/L with p-value: <0.01). However, there was no difference in potassium levels when comparing groups 1 and 3. At the end of the follow-up, the average difference in eGFR was -3.4 (8.8), -5.3(10.1), and -7.8 (11.2) mL/min per 1.73 m2 in groups 1, 2, and 3, respectively, without a statistically significant difference between groups. CONCLUSIONS: In this real-world experience in our community setting, the combination of SGLT2 inhibitors and finerenone in our adult patients with CKD was associated with a very significant and clinically relevant reduction in UACR, without an increased risk of hyperkalemia. Combination therapy of SGLT2 inhibitor and finerenone regarding background use of ACEi/ARB is feasible and should be encouraged for further albuminuria reductions in CKD patients.

Mendelian randomization analysis revealed that albuminuria is the key factor affecting socioeconomic status in CKD patients.

Previous studies indicate a strong correlation between the incidence of chronic kidney disease (CKD) and lower economic status. However, these studies often struggle to delineate a clear cause-effect relationship, leaving healthcare providers uncertain about how to manage kidney disease in a way that improves patients' financial outcomes. Our study aimed to explore and establish a causal relationship between CKD and socioeconomic status, identifying critical influencing factors. We utilized summary meta-analysis data from the CKDGen Consortium and UK Biobank. Genetic variants identified from these sources served as instrumental variables (IVs) to estimate the association between CKD and socioeconomic status. The presence or absence of CKD, estimated glomerular filtration rate (eGFR), and albuminuria were used as exposures, while income and regional deprivation were analyzed as outcomes. We employed the R packages 'TwoSampleMR' and 'Mendelianrandomization' to conduct both univariable and multivariable Mendelian randomization (MR) analyses, assessing for potential pleiotropy and heterogeneity. Our univariable MR analysis revealed a significant causal relationship between high levels of albuminuria and lower income (OR = 0.84, 95% CI: 0.73-0.96, p = 0.013), with no significant pleiotropy detected. In the multivariable MR analysis, both CKD (OR = 0.867, 95% CI: 0.786-0.957, p = 0.0045) and eGFR (OR = 0.065, 95% CI: 0.010-0.437, p = 0.0049) exhibited significant effects on income. This study underscores that higher albuminuria levels in CKD patients are associated with decreased income and emphasizes the importance of effective management and treatment of albuminuria in CKD patients to mitigate both social and personal economic burdens.

Potential kidney protective effects of glucagon-like peptide-1 receptor agonists.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes (T2DM) with chronic kidney disease (CKD). This class of medication has demonstrated promising results in reducing albuminuria, preserving estimated glomerular filtration rate (eGFR), and mitigating cardiovascular (CV) risk, making them potential therapeutic options for individuals with CKD. The kidney protective effects of GLP-1RAs extend beyond glycaemic control, and are thought to be attributed to their anti-inflammatory, antioxidant, and natriuretic properties. Despite these promising findings, the use of GLP-RAs has yet to be definitively shown to slow progression to chronic kidney failure, or reduce CV and kidney related death in people with T2DM and CKD. The Research Study to See How Semaglutide (a once weekly subcutaneous administered GLP-1RA) Works Compared to Placebo in People with Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) was recently stopped because of efficacy. The primary end point for the FLOW trial consists of a composite endpoint of (i) onset of chronic kidney failure; (ii) death from kidney failure; (iii) cardiovascular death; and (iv) onset of a persistent ≥50% reduction in eGFR from baseline. It has also been reported by the sponsors of the trial that the primary end point of the trial was reduced by 24% with both CKD and CV outcomes contributing to risk reduction. In anticipation of the results of the FLOW trial being published, we review the current evidence surrounding kidney outcomes and proposed kidney protective pathways associated with GLP-1RA use.

The impact of mild and moderate COVID-19 infection on the progression of kidney dysfunction in patients with IgA nephropathy.

Background: Previous research indicates that coronavirus disease 2019 (COVID-19) infection may have a role in triggering immunoglobulin A (IgA) nephropathy. However, limited research has explored the clinical implications of COVID-19 infection in individuals already diagnosed with IgA nephropathy. This study aimed to determine whether COVID-19 infection independently affects the subsequent trajectory of kidney function in IgA nephropathy patients. Methods: This was a single-center cohort study. The study included 199 patients diagnosed with IgA nephropathy. The COVID-19 infection status was determined using a combined method: a questionnaire and the Health Code application, both administered at the end of 2022 in northern China. Kidney function trajectory was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum creatinine levels measured during follow-up outpatient visits. The primary endpoint of interest was the eGFR trajectory. Results: Out of the 199 participants, 75% (n = 181) reported a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, determined through antigen or polymerase chain reaction tests, accounting for 79% (n = 143) of the infected patients. A significant majority (98%) experienced mild to moderate symptoms. Over a median follow-up period of 10.7 months post-COVID-19 infection, notable clinical events included gross hematuria in 30 patients (16.6%), which normalized within an average of 3 days. Additionally, a 2-fold increase in proteinuria or progression to the nephrotic range was observed in 10 individuals (5.5%). No cases of acute kidney injury were noted. COVID-19 exposure was associated with an absolute change in eGFR of 2.98 mL/min/1.73 m2 per month (95% confidence interval 0.46 to 5.50). However, in a fully adjusted model, the estimated changes in eGFR slope post-COVID-19 were -0.39 mL/min/1.73 m2 per month (95% confidence interval -0.83 to 0.06, P = .088) which included the possibility of no significant effect. Notably, a higher rate of kidney function decline was primarily observed in patients with a baseline eGFR <45 mL/min/1.73 m2 [-0.56 mL/min/1.73 m2 (-1.11 to -0.01), P = .048]. In the cohort, there were few instances of severe COVID-19 cases. The absence of long-term follow-up outcomes was observed. Conclusions: Overall, mild to moderate COVID-19 infection does not appear to significantly exacerbate the subsequent decline in kidney function among IgA nephropathy patients, particularly in those with preserved baseline kidney function.

Long-term outcomes of adults with FSGS in the German Chronic Kidney Disease cohort.

Background: Focal segmental glomerulosclerosis (FSGS) can lead to kidney failure in adults. This study examines the progression of FSGS in the German Chronic Kidney Disease (GCKD) cohort. Methods: The GCKD study (N = 5217), a prospective cohort, included 159 patients with biopsy-confirmed FSGS recruited from 2010 to 2012. Baseline was defined as the first study visit. Adjudicated endpoints included a composite kidney endpoint (CKE), including an estimated glomerular filtration rate (eGFR) decrease >40%, eGFR <15 ml/min/1.73 m2 or initiation of kidney replacement therapy and combined major adverse cardiovascular events (MACE), including non-fatal myocardial infarction or stroke and all-cause mortality. Associations between baseline demographics, laboratory data, comorbidity and CKE and MACE were analysed using the Cox proportional hazards regression model. Results: The mean age at baseline was 52.1 ± 13.6 years, with a disease duration of 4.72 years (quartile 1: 1; quartile 3: 6) before joining the study. The median urinary albumin:creatinine ratio (UACR) at baseline was 0.7 g/g (IQR 0.1;1.8), while mean eGFR was 55.8 ± 23 ml/min/1.73 m2. Based on clinical and pathological features, 69 (43.4%) patients were categorized as primary FSGS, 55 (34.6%) as secondary FSGS and 35 (22%) as indeterminate. Over a follow-up of 6.5 years, 44 patients reached the composite kidney endpoint and 16 individuals had at least one MACE. UACR ≥0.7 g/g was strongly associated with both the composite kidney endpoint {hazard ratio [HR] 5.27 [95% confidence interval (CI) 2.4-11.5]} and MACE [HR 3.37 (95% CI 1.05-10.82)] compared with <0.7 g/g, whereas a higher eGFR at baseline (per 10 ml/min) was protective for both endpoints [HR 0.8 (95% CI 0.68-0.95) and HR 0.63 (95% CI 0.46-0.88), respectively]. Patients with secondary FSGS experienced a greater rate of eGFR decline than patients with primary FSGS. Conclusions: Lower eGFR and higher albuminuria are key risk factors for kidney disease progression and cardiovascular events in patients with FSGS.

Persistent albuminuria and chronic kidney disease in adults with sickle cell anaemia: Results from a multicenter natural history study.

Clinical and laboratory correlates of chronic kidney disease (CKD) in sickle cell anaemia remain incompletely defined. In a multicenter cohort study, we evaluated the prevalence of persistent albuminuria (PA) and characteristics associated with PA, albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) using logistic, linear and multinomial regression models, respectively. Of 269 participants (median age: 30 years; 57.2% females), the prevalence of PA was 35.7%. Using baseline ACR values of <100 and ≥100 mg/g, the probabilities of PA were 30.0% and 94.6%, respectively. In multivariable logistic regression analyses, male sex (ß = 0.80 [SE = 0.36], p = 0.024) and ACE inhibitors/ARBs use (ß = 1.54 [SE = 0.43], p < 0.001) were associated with higher likelihoods of PA, while higher haemoglobin (ß = -0.33 [SE = 0.13], p = 0.009) and HbF (ß = -0.04 [SE = 0.02], p = 0.041) were associated with lower likelihoods of PA. In multivariable multinomial regression analyses, older age (ß = 0.06 [SE = 0.02], p = 0.004) and higher alkaline phosphatase (ß = 0.01 [SE = 0.00], p = 0.004) were associated with higher odds of having eGFR 60-90 versus eGFR>90 mL/min/1.73 m2 using the cystatin C-based CKD-EPI-2012 equation. Additionally, higher systolic blood pressure (ß = 0.11 [SE = 0.03], p = 0.001) and blood urea nitrogen (ß = 0.45 [SE = 0.12], p < 0.001) were associated with higher odds, while higher haemoglobin (ß = -1.22 [SE = 0.43], p = 0.004) was associated with lower odds of having eGFR<60 versus eGFR>90 mL/min/1.73 m2. PA and decreased eGFR are associated with measures of disease severity and comorbid conditions (Clinicaltrials.gov Identifier: NCT03277547).

Normoalbuminuria-is it normal? The association of urinary albumin within the 'normoalbuminuric' range with adverse cardiovascular and mortality outcomes: A systematic review and meta-analysis.

AIM: To assess the association between urinary albumin-to-creatinine ratio (UACR) categories within the normal range with mortality and adverse cardiovascular outcomes. MATERIALS AND METHODS: PubMed and Embase were systematically searched for real-world evidence studies. Studies were manually evaluated according to predefined eligibility criteria. We included prospective and retrospective cohort studies of the association between UACR categories <30 mg/g and cardiovascular outcomes or mortality. Published information regarding study design, participants, UACR categorization, statistical methods, and results was manually collected. Two UACR categorization approaches were defined: a two-category (UACR <10 mg/g vs. 10-30 mg/g) and a three-category division (UACR <5 mg/g vs. 5-10 and 10-30 mg/g). A random effects meta-analysis was performed on studies eligible for the meta-analysis. RESULTS: In total, 22 manuscripts were identified for the systematic review, 15 of which were eligible for the meta-analysis. The results suggest an association between elevated UACR within the normal to mildly increased range and higher risks of all-cause mortality, cardiovascular death, and coronary heart disease, particularly in the range of 10-30 mg/g. Compared with UACR <10 mg/g, the hazard ratio [HR (95% confidence interval, CI)] for UACR between 10 and 30 mg/g was 1.41 (1.15, 1.74) for all-cause mortality and 1.56 (1.23, 1.98) for coronary heart disease. Compared with UACR <5 mg/g, the risk of cardiovascular mortality for UACR between 10 and 30 mg/g was more than twofold [HR (95% CI): 2.12 (1.61, 2.80)]. Intermediate UACR (5-10 mg/g) was also associated with a higher risk of all-cause mortality [HR (95% CI): 1.14 (1.05, 1.24)] and cardiovascular mortality [HR (95% CI): 1.50 (1.14, 1.99)]. CONCLUSIONS: We propose considering higher UACR within the normoalbuminuric range as a prognostic factor for cardiovascular morbidity and mortality. Our findings underscore the clinical significance of even mild increases in albuminuria.

Chronic Kidney Disease Study in Diabetic Patients: Insights From Primary Care Units in Northern Portugal.

Introduction Diabetes mellitus (DM) remains a primary cause of morbidity and mortality, leading to complications such as blindness, kidney failure, and lower limb amputations. Early detection of kidney damage, indicated by microalbuminuria (MA), is crucial for managing DM. Given the impact of these conditions, evaluating the prevalence of chronic kidney disease (CKD) in diabetic populations within primary healthcare is essential. Methodology This was a cross-sectional and observational study. Adults diagnosed with DM type 1 or 2, from five primary care units (PCUs) located in the North of Portugal, were included in this study. Descriptive and correlational statistics were performed using IBM SPSS Statistics for Windows, Version 28.0 (IBM Corp., Armonk, NY). Statistical significance was set to P < 0,05. Logistic regression models were created to identify the factors associated with CKD and DM. Results A sample of 357 diabetic patients was obtained, with 166 (46.5%) females. Of the sample, 250 (70.1%) were aged 65 or older, and the median known duration of DM was 9.36 years. Excess weight or obesity accounted for 79.8%, with a median body mass index of 28.73 kg/m2 and hypertension in 284 (79.6%). An estimated glomerular filtration rate (eGFR) less than 60 mL/min was present in 89 (24.9%) and an MA of 30 mg/dL or higher was present in 68 (19.0%). In total, 130 (36.4%) individuals exhibited eGFR and MA consistent with CKD. Among these, 25 (78.1%) had other identifiable causes of CKD besides DM, hypertension, overweight, or obesity. Binary logistic regression models were constructed to find a relationship between CKD with eGFR < 60 mL/min and MA. A statistically significant association was found between CKD with eGFR < 60 mL/minute and age (odds ratio [OR] = 1.150; P < 0.001), kidney stones (OR = 5.112; P = 0.003), absence of excess weight or obesity (OR = 0.267; P < 0.001). The use of GLP1 agonists showed statistical significance as a predictor (OR = 4.653; P = 0.042) of the presence of MA. Discussion The study investigates the impact of DM and its complications in the surveyed population. While most patients had controlled DM (284, 76.2%), prolonged disease duration correlated with poorer glycemic control, underscoring the need for more effective management strategies in advanced disease stages. Notably, a third of individuals with DM had CKD, with significant implications for therapeutic interventions and heightened risks of renal failure and cardiovascular morbidity. MA was a crucial marker for endothelial injury, with prevalence influenced by DM duration and medication type. However, in many cases, correct identification of CKD was lacking, suggesting under-recognition of renal deterioration in DM. While the study offers valuable insights, its limited sample size and geographic scope warrant cautious interpretation, emphasizing the need for broader, context-specific research to inform comprehensive healthcare strategies. Conclusions In conclusion, this study highlights the significant burden of CKD among diabetic patients, emphasizing the need for proactive screening, personalized management, and accurate diagnosis. Despite limitations, it underscores the importance of early detection and tailored interventions, advocating for improved diabetes care to mitigate renal complications on a broader scale.

[Association Between the Aggregate Index of Systemic Inflammation and Albuminuria: A Cross-Sectional Study of National Health and Nutrition Examination Survey 2007-2018]. / å ¨èº«ç‚Žç—‡ç»¼åˆæŒ‡æ•°ä¸Žç™½è›‹ç™½å°¿çš„å ³è”ï¼šåŸºäºŽ2007­2018å¹´å›½å®¶å¥åº·ä¸Žè¥å »è°ƒæŸ¥çš„æ¨ªæ–­é¢ç ”ç©¶.

Objective: Prior studies have established a connection between albuminuria and various inflammatory reactions, highlighting that an increase in C-reactive protein by 1 mg/L increases the likelihood of albuminuria by 2%. Recent investigations indicate a positive correlation between the systemic immune-inflammation index (SII) and increased urinary protein excretion. In addition, elevated levels of the systemic inflammatory response index (SIRI) also correlate with a higher prevalence of albuminuria. The aggregate index of systemic inflammation (AISI) offers a more comprehensive indicator of inflammation, providing an extensive assessment of systemic inflammatory status compared to SII and SIRI. Yet, the specific relationship between AISI and albuminuria remains unclear. This study aims to explore this association in U.S. adults. Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) for 2007-2018, excluding pregnant women and individuals under 18. Cases with missing data on AISI, urinary albumin concentration, and other covariates were also excluded. AISI was computed using the formula: AISI=(platelet count×neutrophil count×monocyte count)/lymphocyte count. Albuminuria was defined as the urinary albumin-to-creatinine ratio exceeding 30 mg/g. Continuous variables were presented in the form of the mean±standard error, and categorical variables in percentages. We utilized weighted t-tests and chi-square tests for baseline comparisons. We applied weighted multivariable logistic regression and generalized additive models (GAM) to explore the association between AISI and albuminuria and to assess potential nonlinear relationships. Results: The study included 32273 participants, with an average age of (46.75±0.24) years old. The cohort comprised 48.73% males and 51.27% females. The prevalence of albuminuria was 9.64%. The average logarithmic value of log2AISI was 7.95±0.01, and were categorized into tertiles as follows: Quartile 1 (Q1) (4.94 to 7.49), Q2 (7.49 to 8.29), and Q3 (8.29 to 10.85). As log2AISI increased, so did the prevalence of hypertension, diabetes, congestive heart failure, and albuminuria, all showing statistically significant increases (P<0.001). Similarly, the use of antihypertensive, lipid-lowering, and hypoglycemic drugs was also more prevalent (P<0.001). Statistically significant differences were observed across the three groups concerning age, race and ethnicity, formal education, alcohol consumption, smoking status, systolic and diastolic blood pressures, body mass index, estimated glomerular filtration rate, HbA1c, alanine aminotransferase, aspartate aminotransferase, albumin, creatinine, uric acid, and high-density lipoprotein cholesterol (P<0.05). However, no significant differences were noted in the total cholesterol or the sex ratios among the groups. The association between log2AISI and albuminuria was assessed using weighted multivariable logistic regression, and the detailed results are presented in Table 2. In model 1, without adjusting for covariates, each unit increase in log2AISI was associated with a 32% increase in the risk of albuminuria (odds ratio [OR]=1.32, 95% confidence interval [CI]: 1.27-1.38, P<0.001). Model 2 was adjusted for age, gender, race, and education level, and showed a similar trend, with each unit increase in log2AISI associated with a 31% increased risk (OR=1.31, 95% CI: 1.26-1.37, P<0.001). Model 3, which was further adjusted for all covariates, revealed that each unit increase in log2AISI was associated with a 20% increase in the risk of albuminuria (OR=1.20, 95% CI: 1.15-1.26, P<0.001). The study also transformed log2AISI from a continuous to a categorical variable for analysis. Compared with Q1, the risk of albuminuria in Q3, after adjusting for all covariates, significantly increased (OR=1.37, 95% CI: 1.22-1.55, P<0.001). Q2 also demonstrated a higher risk compared with Q1 (OR=1.13, 95% CI: 1.06-1.36, P=0.004). The trend test indicated a dose-effect relationship between increasing log2AISI and the rising risk of albuminuria. GAM revealed a nonlinear relationship between log2AISI and albuminuria, with distinct trends noted between sexes. Segmented regression based on turning points showed significant effects among women, although the slope difference between the segments was not significant. In men, a significant threshold effect was observed; below the log2AISI of 7.25, increases in log2AISI did not enhance the risk of albuminuria, but above this threshold, the risk significantly increased. As part of a sensitivity analysis, weighted multivariable logistic regression was performed by changing the outcome variable to macroalbuminuria and adjusting for all covariates. The analysis showed that for every unit increase in log2AISI, the risk of developing macroalbuminuria increased by 31% (OR=1.31, 95% CI: 1.15-1.49, P<0.001). Compared with Q1, the risk of albuminuria in Q3 increased by 69% (OR=1.69, 95% CI: 1.27-2.25, P<0.001), and in Q2, it increased by 40% (OR=1.40, 95% CI: 1.03-1.92, P=0.030). Subgroup analysis and interaction results showed that the positive association between AISI and proteinuria risk was stronger in men than in women. Similarly, the association was stronger in people with hypertension compared with those with normal blood pressure, and higher in overweight people compared with those of normal weight. Furthermore, smokers and drinkers showed a stronger positive association between AISI and the risk of proteinuria than non-smokers and non-drinkers do. These results suggest that sex, blood pressure, body mass index, smoking, and alcohol consumption interact with AISI to influence the risk of proteinuria. Conclusion: There is a robust positive association between AISI and increased risks of albuminuria in US adults. As log2AISI increases, so does the risk of albuminuria. However, further validation of this conclusion through large-scale prospective studies is warranted.

The potassium puzzle: exploring the intriguing connection to albuminuria.

Background: Studies have revealed a relationship between dietary potassium intake and albuminuria, despite the fact that the human body needs a lot of potassium. Our study concentrated on the link between dietary potassium intake and albuminuria. Methods: This study used subgroup analysis and weighted multivariate regression analysis. Data from the National Health and Nutrition Examination Survey (NHANES) were examined to determine the urinary albumin-to-creatinine ratio (ACR) and participant age (20 years or older). ACR >30 mg/g was the threshold for albuminuria. Results: 7,564 individuals in all were included in the study. The link between the two was significant in both our original model (OR = 0.99; 95% CI, 0.98-0.99, p < 0.0001) and the minimum adjusted model (OR = 0.99; 95% CI, 0.98-0.99, p < 0.0001). A fully adjusted model did not change the significance of the negative correlation between potassium consumption and albuminuria (OR = 0.99; 95% CI, 0.98-1.00, p = 0.0005), indicating that each unit increase in potassium intake was related with a 1% decrease in the chance of developing albuminuria. The negative correlation between potassium intake and albuminuria was not significantly influenced by sex, age, BMI, hypertension, diabetes, or smoking, according to interaction tests (p for interaction >0.05). Conclusion: Reduced risk of albuminuria was linked to higher dietary potassium intake. The particular mechanism linking the two still has to be explained by several inventive and prospective studies.

Congestion as a crucial factor determining albuminuria in patients with cardiorenal disease.

Background: Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. Methods: This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. Results: The median age was 74 years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30-300 mg/g and 64 (7.4%) had a UACR >300 mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R2 = 57.6%), systolic blood pressure (R2 = 21.1%), previous furosemide equivalent dose (FED; R2 = 7.5%), antigen carbohydrate 125 (CA125; R2 = 6.1%), diabetes mellitus (R2 = 5.6%) and oedema (R2 = 1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. Conclusions: In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria.

The relationship between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus.

OBJECTIVE: Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM). DESIGN, PATIENTS AND MEASUREMENTS: This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia. RESULTS: The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = -.117, r = -.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76-7.52, p = .001). CONCLUSION: Albuminuria is more frequently observed in patients with hypomagnesemia.