Risk Factors For Albuminuria Research Articles

Higher Risk of Proteinuria with Atezolizumab plus Bevacizumab than Lenvatinib in First-Line Systemic Treatment for Hepatocellular Carcinoma

Introduction: Proteinuria presents a challenging complication during systemic therapy for hepatocellular carcinoma (HCC). This study aims to identify risk factors for proteinuria in patients with HCC treated with atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first-line systemic treatment. Methods: A retrospective analysis was conducted on 622 consecutive patients with unresectable HCC who received Atezo/Bev or LEN as first-line systemic treatment between October 2013 and October 2022. Cumulative incidence of proteinuria was estimated using Kaplan-Meier curves and compared using log-rank tests. Risk factors for proteinuria were identified using Cox proportional-hazard models, along with propensity score-matched and subgroup analyses. Results: Among 367 patients treated with Atezo/Bev and 255 with LEN, the cumulative incidence of proteinuria at 12 months was 27.5%. In the multivariable analysis, Atezo/Bev treatment (adjusted HR [aHR]: 1.57; 95% CI: 1.03–2.42), diabetes (aHR: 1.64; 95% CI: 1.03–2.61), hypertension (aHR: 2.27; 95% CI: 1.04–4.97), Child-Pugh class B (aHR: 3.43; 95% CI: 1.34–8.78), macrovascular invasion (MVI; aHR: 1.58; 95% CI: 1.04–2.38), and an estimated glomerular filtration rate ≤60 mL/min/1.73 m2 (aHR: 3.21; 95% CI: 1.84–5.62) were identified as risk factors for proteinuria. A higher risk of proteinuria in Atezo/Bev patients compared with LEN was consistently observed in the PS-matched cohort, particularly pronounced in subgroups with MVI (HR: 2.84; 95% CI: 1.23–6.54) compared with those without MVI (HR: 1.31; 95% CI: 0.69–2.47). Conclusions: Patients treated with Atezo/Bev as first-line systemic treatment for HCC exhibited a higher risk of proteinuria compared with those with LEN, particularly when accompanied by MVI.

Snoring and Self-Reported Apnea Are Risk Factors for Albuminuria and CKD: A Retrospective Data Analysis

Snoring and Self-Reported Apnea Are Risk Factors for Albuminuria and CKD: A Retrospective Data Analysis

The Relationship between Serum Sodium Concentration and Albuminuria: A Retrospective Cohort Study.

Lowering dietary salt intake reduces albuminuria, an early marker of renal damage and a sensitive predictor of adverse cardiovascular outcomes. The mechanisms underlying this effect are uncertain but small changes in serum sodium concentration may be important: this retrospective cohort study investigated the hypothesis that higher serum sodium concentration is a risk factor for albuminuria (defined as a urine albumin:creatinine ratio [UACR], ≥3 mg/mmol). Primary care data from the Royal College of General Practitioners Research and Surveillance Centre were used to identify 47,294 individuals with a UACR result available between April 2010 and March 2015, and no known albuminuria prior to this. Exclusion criteria were missing or abnormal serum sodium concentration at baseline (<135 or >146 mmol/L); age <18 years; diabetes mellitus; decompensated liver disease; heart failure; and stage 5 chronic kidney disease. After adjustment for known risk factors, there was a significant "U-shaped" relationship between serum sodium concentration and albuminuria. The lowest risk was associated with a serum sodium of 138-140 mmol/L. In comparison, the risk of albuminuria was 18% higher with a serum sodium of 135-137 mmol/L and 19% higher with a serum sodium of 144-146 mmol/L. There was no association between serum sodium concentration and blood pressure. The finding of a positive association between higher serum sodium concentration and albuminuria is in support of the hypothesis, but the inverse relationship between serum sodium concentration and albuminuria at lower concentrations warrants further explanation.

Prevalence of proteinuria after living donor kidney transplantation and related risk factors: A retrospective cohort study from Syria

Introductionproteinuria is associated with poor allograft and patient survival in kidney transplant recipients (KTRs). This study aims to investigate the prevalence and risk factors of proteinuria in KTRs and its impact on kidney function during the first two years after kidney transplantation (KT). Materials and methods200 KTRs were included in this retrospective cohort study from living donors, performed in two University hospitals in Syria, from January 2018 to March 2021. Demographic and immunological characteristics were analyzed depending on the 24 h urine protein (Up) excretion that was classified into three groups: Up I (150–500 mg/day), Up II between (0.5–1 g/day), and Up III (>1 g/day). ResultsUp was increased subsequently as the transplant progressed, where the greatest excretion of the Up was reported 2 years after KT. At 6 months after KT; the cold ischemic time (CIT), serum creatinine (Cr), using angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin II receptor blockers (ARBs), and GFR showed strong significant differences between Up groups (P = 0.00003, 0.0001, 0.00001, and 0.026; respectively). The CIT and Cr were higher in the Up III group compared to Up I and UP II groups. At 12 months after KT; Cr, using ACEIs/ARBs, and GFR showed strong significant differences between Up groups (P = 0.00009, <0.0001, and <0.0001; respectively). The mean Cr was higher in Up II and Up III groups (1.7 mg/dL; for each) compared to the Up I group (1.0 mg/dL). At 24 months after KT; CIT, using ACEIs/ARBs, Cr, and GFR showed strong significant differences between Up groups (P = 0.02, <0.0001, 0.00008, and <0.0001; respectively). ConclusionThis is the first study from Syria that conducted in KT patients. The prevalence and amount of proteinuria showed subsequently increased as the transplant progressed. Serum Cr, GFR, CIT, and using ACEIs/ARBs showed differences between Up groups at 6 months, 1 year, and 2 years after KT. Our data suggest that the use of ACEIs/ARBs is not a contraindication in early posttransplant period. Due to several known cardiovascular and renal benefits of ACEIs/ARBs future studied in KT population should investigated to determine if these drugs could give beneficial effects on grafts and patients survival.

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

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. 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. The median age was 74years, 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 30-300mg/g and 64 (7.4%) had a UACR >300mg/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. 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.

Prevalence and management of proteinuria associated with vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitor treatment in advanced renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer.

Vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors (VEGFR-TKIs) are often used for treatment of several types of cancer; however, they are associated with an increased risk of proteinuria, sometimes leading to treatment discontinuation. We searched PubMed and Scopus to identify clinical studies examining the incidence and risk factors for proteinuria caused by VEGFR-TKIs in patients with renal cell carcinoma, thyroid cancer, and hepatocellular carcinoma. The global incidence of proteinuria ranged from 6% to 34% for all grades of proteinuria, and from 1% to 10% for grade ≥3 proteinuria. The incidence of proteinuria did not differ significantly by cancer type, but in all three cancer types, there was a trend toward a higher incidence of proteinuria with lenvatinib than with other VEGFR-TKIs. In terms of risk factors, the incidence of proteinuria was significantly higher among Asians (including Japanese) compared with non-Asian populations. Other risk factors included diabetes mellitus, hypertension, and previous nephrectomy. When grade 3/4 proteinuria occurs, patients should be treated according to the criteria for dose reduction or withdrawal specified for each drug. For grade 2 proteinuria, treatment should be continued when the benefits outweigh the risks. Referral to a nephrologist should be considered for symptoms related to decreased renal function or when proteinuria has not improved after medication withdrawal. These management practices should be implemented universally, regardless of the cancer type.

Association of serum syndecan-1 concentrations with albuminuria in type 2 diabetes.

Syndecan (SDC)-1 is a transmembrane heparan sulfate proteoglycan and is a major component of endothelial glycocalyx (EG). This study aimed to investigate the association of serum SDC-1 concentration as a marker of EG degradation with albuminuria in type 2 diabetes. We included 370 patients with type 2 diabetes and 219 individuals with no diabetes. The individuals with estimate glomerular filtration rate <30mL/min/1.73m2 were excluded. Serum SDC-1 concentration was higher in type 2 diabetes than in no diabetes. The presence of diabetes was independently associated with log [SDC-1] in multivariate analysis. In type 2 diabetes, serum SDC-1 concentration was correlated with log [urinary albumin-to-creatinine ratio (ACR)]. Moreover, log [SDC-1] was an independent determinant of log [ACR] after adjustment for known risk factors of albuminuria. Serum SDC-1 concentration was higher in patients with type 2 diabetes compared to individuals with no diabetes and an independent determinant of ACR. This study implicates the role of the EG degradation in albuminuria in type 2 diabetes.

Thyroid function and thyroid homeostasis parameters are associated with increased urinary albumin excretion in euthyroid individuals over 60 years old from NHANES.

The relationship between thyroid function/homeostasis parameters and renal function has been extensively studied. However, the relationship between thyroid function and thyroid homeostasis parameters with albuminuria among elderly individuals remains unclear. The population was divided into an albuminuria group and a non-albuminuria group for baseline characteristic difference analysis. Multivariable logistic regression was used to test the association between thyroid function, and thyroid homeostasis parameters and albuminuria. The nonlinear relationship was explored with restricted cubic splines. Meanwhile, we investigated whether the relationship also existed in the diabetes and hypertension subgroups. Receiver operating characteristic (ROC) curves were used to assess the effectiveness of the indices. FT4 and TFQIFT4 were positively correlated with albuminuria (OR = 1.12; 95% CI = 1.02-1.23, p = 0.02; OR = 1.79; 95% CI = 1.08-2.99, p = 0.03), and FT3/FT4 was negatively correlated with albuminuria (OR = 0.03; 95% CI = 0.00-0.26, p = 0.003). Additionally, the nonlinear relationship between FT3/FT4 as well as TSHI and albuminuria was approximately U-shaped. Similar results were observed in the hypertension subgroup but not in the diabetes subgroup. There was a U-shaped nonlinear relationship between FT3 and albuminuria in the diabetes group. In addition, FT3/FT4 performed better than TFQI, TT4RI, and TSHI in ROC analyses for albuminuria prediction. FT4, TFQIFT4, and a low FT3/FT4 ratio were risk factors for albuminuria in euthyroid individuals over 60 years old. However, FT3 was more associated with albuminuria in the diabetes subgroup. TSH was not associated with albuminuria in any analysis. In our study, we attempted to provide more reasonable thyroid parameters and basis for evaluating patients with underlying albuminuria. FT3/FT4 may be used as a helpful indicator to predict albuminuria and provide novel ideas for the evaluation and treatment of albuminuria.

ЭФФЕКТИВНОСТЬ ТЕРАПИИ ИНГИБИТОРАМИ АНГИОТЕНЗИН- ПРЕВРАЩАЮЩЕГО ФЕРМЕНТА В ПРОФИЛАКТИКЕ РАЗВИТИЯ ПРОТЕИНУРИИ У МАЛЬЧИКОВ С Х-СЦЕПЛЕННЫМ СИНДРОМОМ АЛЬПОРТА: ДАННЫЕ ОДНОЦЕНТРОВОГО КОГОРТНОГО НЕРАНДОМИЗИРОВАННОГО ИССЛЕДОВАНИЯ

Patients with a hemizygous mutation in the COL4A5 gene have a high risk of developing renal failure at a young age. Proteinuria reflects the progression of glomerulopathy in Alport syndrome (AS). In order to improve renal survival in AS patients with proteinuria are prescribed with angiotensin system inhibitors. There is a limited, insufficient number of studies demonstrating the effectiveness of angiotensin-converting enzyme inhibitors (ACEI) in children with AS; the therapeutic effect initiated prior to the development of proteinuria has not been studied as yet. The purpose of the research was to determine the effectiveness of ACEI therapy in the form of enalapril in the prevention of proteinuria in boys with X-linked AS (XLAS). Materials and methods used: boys aged 2 to 15 y/o with genetically confirmed XLAS were included in a single-center prospective cohort study. Enalapril was prescribed at doses of 1 to 3 mg/m2/day. Urinary protein excretion (Pr) and estimated glomerular filtration rate (eGFR) were studied at the time of inclusion and with a frequency of one time per six months for the three-year period or longer. The primary endpoint was the time of onset of proteinuria. Results: 72 boys in total, incl. 29 without proteinuria, who received enalapril therapy (Group 1, age 6.2±1.9 y/o, Pr 67±20 mg/m2/day, eGFR 118±15.2 ml /min/1.73 m2) and 43 children without therapy (Group 2, age 6.8±1.9 y/o, Pr 87±23 mg/m2/day, eGFR 119±17.3 ml/min/1.73 m2). The incidence of proteinuria (0.45 in G1 vs. 0.98 in G2, p&lt;0.001), incl. up to the age of 10 y/o (0.42 vs 0.91, respectively, p&lt;0.001) was statistically significantly lower in G1. Proteinuria developed later in the treatment group (10.2±2.9 vs. 4.9±1.4 years, p=0.300). Non-missense mutations in the COL4A5 gene, episodes of macrohematuria in records and lack of therapy were the risk factors for proteinuria; the lack of enalapril therapy was a predictor for proteinuria. The risk of proteinuria during therapy was reduced by 50% (RR=0.46 (95% CI 0.31; 0.68); ARR=0.53; NNT=1.9). Conclusion: initiation of enalapril therapy at the pre-proteinuria stage of nephropathy in boys with XLAS reduces the risk of proteinuria preventing its occurrence in every 50$ of cases when receiving treatment. Early initiation of therapy may be effective in preventing the progression of kidney disease in boys with XLAS.

433-P: Syndecan-1, a Marker of Endothelial Glycocalyx Degradation, Is Associated with Albuminuria in Type 2 Diabetes

The endothelial glycocalyx (EG) covers the luminal surface of vascular endothelium and is involved in various functions of endothelium including the microvascular permeability. Syndecan (SDC)-1 is a transmembrane heparan sulfate proteoglycan and is a major component of EG. Since the extracellular domain of SDC-1 is shed by inflammatory mediators, increased circulating levels of SDC-1 is considered as a marker of EG degradation. No study has thus far investigated the relationship between EG degradation and albuminuria in type 2 diabetes. This study aimed to investigate the association between EG degradation assessed by serum SDC-1 levels and urinary albumin to creatinine ratio (ACR) in type 2 diabetes. This study enrolled 370 Japanese patients with type 2 diabetes (T2D) and 219 nondiabetic controls (ND). Patients with severe kidney dysfunction whose estimate glomerular filtration rate (eGFR) was less than 30 mL/min/1.73m2 were excluded. T2D patients were divided into normoalbuminuria (A1), microalbuminuria (A2) and macroalbuminuria (A3) by ACR. Median value of serum SDC-1 levels in T2D with A1 stage was 24.5 ng/mL which was higher than that in ND (16.0 ng/mL) (p &amp;lt;0.001). Median values of SDC-1 in T2D with A2 and A3 stages were 29.0 and 38.7 ng/mL, respectively, which were significantly different among albuminuria stages (p &amp;lt;0.001). First, multivariate analysis including T2D patients with A1 stage and ND revealed that the presence of T2D was independently associated with serum SDC-1 level (β = 0.356, p &amp;lt;0.001). Next, multivariate analysis in T2D patients with all albuminuria stages revealed that serum SDC-1 level was independently associated with ACR (β = 0.121, p = 0.012) after adjustment for known other risk factors for albuminuria. In conclusion, serum SDC-1 level is increased in T2D compared to ND and is an independent determinant of ACR in T2D patients. This study suggests a potential involvement of the EG degradation in albuminuria in T2D. Disclosure Y. Kakutani: None. T. Morioka: None. Y. Yamazaki: None. A. Ochi: None. S. Fukumoto: None. T. Shoji: Research Support; Ono Pharmaceutical Co., Ltd., Bayer Inc. Other Relationship; Kowa Company, Ltd. M. Emoto: None.

Traditional Chinese medicine body constitution predicts new-onset diabetic albuminuria in patients with type 2 diabetes: Taichung diabetic body constitution prospective cohort study

This prospective cohort study explored whether body constitution (BC) independently predicts new-onset albuminuria in persons with type 2 diabetes mellitus (T2DM) enrolled in the diabetes care management program (DCMP) of a medical center, providing evidence of integrating traditional Chinese medicine into DCMP for improving care quality. Persons with T2DM (n = 426) originally without albuminuria enrolled in DCMP were recruited in 2010 and were then followed up to 2015 for detecting new-onset albuminuria. The participants received urinalysis and blood test annually. Albuminuria was determined by an elevated urinary albumin/creatinine ratio (≥ 30 µg/mg), and poor glucose control was defined as Glycosylated hemoglobin above or equal to 7%. BC type (Yin deficiency, Yang deficiency, and phlegm stasis) was assessed using a well-validated body constitution questionnaire at baseline. Risk factors for albuminuria (sociodemographic factors, diabetes history, lifestyle behaviors, lipid profile, blood pressure, and kidney function) were also recorded. Hazard ratios (HR) of albuminuria for BC were estimated using multivariate Cox proportional hazards model. During the 4-year follow-up period, albuminuria occurred in 30.5% of participants (n = 130). The HR indicated that Yin deficiency was significantly associated with an increased risk of new-onset albuminuria in persons with T2DM and good glucose control after adjustment for other risk factors (HR = 2.09; 95% confidence interval = 1.05-4.17, P = .04), but not in those with poor glucose control. In persons with T2DM and poor glucose control, phlegm stasis was also significantly associated with a higher risk of albuminuria (2.26; 1.03-4.94, P = .04) after multivariate adjustment, but not in those with good glucose control. In addition to already-known risk factors, BC is an independent and significant factor associated with new-onset albuminuria in persons with T2DM. Our results imply Yin deficiency and phlegm stasis interacting with glucose control status may affect new-onset albuminuria in persons with T2DM.

Risk Factors for Early Onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma

Introduction: Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC. Methods: Sixty-four patients with Child-Pugh scores of 5–7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated. Results: The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579–9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614–24.010; p = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133–6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr). Conclusion: Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev.

From Bench to Bedside: Clinical and Biomedical Investigations on Hepatitis C Virus (HCV) Genotypes and Risk Factors for Albuminuria.

An extrahepatic manifestation of nephropathies can be a feature of the chronic hepatitis C virus (HCV) infection. Albuminuria is a major risk factor for nephropathies and chronic kidney disease (CKD). The correlation between HCV genotypes and albuminuria is still unclear. In this study, investigations have been done for the biomedical tools and methodologies used in the National Health and Nutrition Examination Survey (NHANES) public database. We searched the 2007–2016 NHANES public database to retrieve data regarding the different HCV genotypes and clinical scenarios. This study attempted to investigate the impacts of HCV genetic diversity, associated comorbidities, and racial differences on albuminuria. The urine albumin/creatinine ratio (ACR) was the primary endpoint. Among 40,856 participants, 336 participants with positive and 237 with negative HCV RNA tests were analyzed, excluding 14,454 participants with negative HCV antibodies and 25,828 which were missed. After controlling for sex, race, education level, smoking, diabetes mellitus, hepatitis B, alcohol use, and body mass index (BMI) with a generalized linear equation, HCV genotype 2 was more likely than any other genotype to cause albuminuria based on the urine ACR (p < 0.001). The generalized linear equation also demonstrated a significantly higher urine ACR, including hepatitis B (p < 0.001), diabetes mellitus (p < 0.001), and smoking (p = 0.026). In summary, the patients with HCV genotype 2 presented with increased albuminuria in comparison with other HCV genotypes in this 10-year retrospective analysis. HCV infection could be a risk factor of CKD; early diagnosis and appropriate treatment may improve clinical outcomes.

Etiology of Persistent Microalbuminuria in Nigeria (P_MICRO study): protocol and study design

BackgroundMicroalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4–8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and kidney disease, including diabetes, APOL1 high-risk genotype, and smoking were rare. Co-infection with endemic pathogens may also be significant contributors to albuminuria, but co-infections were not evaluated in the R3 study population.MethodsIn Aim 1, we will cross-sectionally compare the prevalence of albuminuria and established kidney disease risk factors in a cohort of PWH to age- and sex-matched HIV-negative adults presenting for routine care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage stored specimens from 2500 R3 participants and enroll an additional 500 PLWH recently initiated on ART (≤ 24 months) and 750 age- and sex-matched HIV-negative adults to determine the contribution of HIV, hypertension, and other comorbid medical conditions to prevalent albuminuria. In Aim 2, we will follow a cohort of 1000 HIV-positive, ART-treated and 500 HIV-negative normoalbuminuric adults for 30 months to evaluate the incidence and predictors of albuminuria.DiscussionThe findings from this study will support the development of interventions to prevent or address microalbuminuria in PWH to reduce kidney and cardiovascular morbidity and mortality. Such interventions might include more intensive monitoring and treatment of traditional risk factors, the provision of renin-angiotensin aldosterone system or sodium-glucose cotransporter-2 inhibitors, consideration of changes in ART regimen, and screening and treatment for relevant co-infections.

Альбумінурія та ВІЛ-інфекція в педіатричних пацієнтів

HIV infection increases the risk of developing chronic kidney disease (CKD). Diagnosis at an early stage of HIV associated kidney disease in children is of particular importance, given its prevalence. Determination of the concentration of albumin and creatinine in a single portion of urine, followed by the calculation of the albumin/creatinine ratio (ACR) is used for early diagnosis and assessment of the progression of CKD. Purpose - to study the frequency and risk factors of albuminuria in children with HIV infection, depending on the stage of the disease, immunosuppression, and viral load. Materials and methods. 73 children with HIV infection were examined. Albumin was analyzed in the morning urine sample twice (during the first and third months of observation) using a Beckman Coulter AU 480 series analyzer. Albuminuria was assessed by ACR. The criterion for a moderately elevated level of albuminuria was considered as ACR ≥3 mg/mmol in both measurements and was interpreted as the presence of microalbuminuria (MAU). Results. A steady increase in ACR was noted in 19 (26.0%) patients. The influence of the stage of HIV-infection on the level of albuminuria has not been established. Non-significant immunosuppression (IS) sharply reduced the chances of MAU - OR=0.019 (CI: 0.002-0.159), the presence of a very severe stage of IS significantly increased them - OR=18.89 (CI: 4.33-82.32). There was a pronounced inverse correlation between the ACR and the CD4+ count, both absolute (ρ=-0.51; p&lt;0.001) and relative (ρ=-0.53; p&lt;0.001). It was found that against the background of viral load, the average ACR was twice as high, and the percentage of MAU was nine times higher. In the case of normal viral overload, the chances of moderately elevated albuminuria were significantly reduced - OR=0.048 (CI: 0.012-0.194). The highest rates of ACR were observed in children with a viral load of more than 100,000 copies of RNA/ml, among these patients, MAU was stated in ¾ of cases. A high viral load increased the risks of MAU by one and a half orders of magnitude - OR=15.30 (CI: 3.51-66.68). Elevated ACR was recorded 3.6 times more often in children with progressive HIV-infection than in other patients (OR=14.13; CI: 1.47-136.12; p&lt;0.02). Conclusions. More than a quarter of children with HIV-infection have moderately elevated albuminuria. Renal dysfunction in children with HIV infection has been most closely associated with very severe immunosuppression, RNA HIV viral load &gt;100,000 copies/ml, and progressive course of HIV-infection, as evidenced by albuminuria studies. The study was carried out in accordance with the principles of the Declaration of Helsinki. The study protocol was adopted by the Local Ethics Committee of the institution specified in the work. The informed consent of the parents or guardians of the children was obtained for the study. The authors declare no conflict of interest. Key words: HIV infection, children, albuminuria, risk factors.

Risk Factors of Proteinuria in Patients with Hepatocellular Carcinoma Receiving Lenvatinib.

Proteinuria is one of the most frequently reported adverse events leading to the discontinuation of lenvatinib treatment in patients with advanced hepatocellular carcinoma (HCC). However, there are no reports regarding the risk factors of proteinuria in patients with HCC or patients receiving lenvatinib. We retrospectively reviewed the medical records of patients with HCC receiving lenvatinib at the Kobe City Medical Center General Hospital between April 2018 and December 2020. The severity of proteinuria was graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A multivariate Cox proportional hazards model was employed to identify the risk factors of developing grade ≥2 proteinuria. Among the 37 patients included, 3 patients had grade-1 proteinuria at baseline and 10 patients had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline. Grades 1, 2, and 3 proteinuria were observed in 15 (40.5%), 10 (27.0%), and 2 (5.4%) patients, respectively, during lenvatinib treatment. The median value of eGFR was significantly lower in patients who developed grade ≥2 proteinuria than those with grade ≤1 proteinuria (59.6 vs. 78.1 mL/min/1.73 m2, p = 0.045). Multivariate analysis revealed that pre-existing proteinuria at baseline (hazard ratio (HR), 9.72; 95% confidence interval (CI), 1.29-52.21; p = 0.030), and eGFR <60 mL/min/1.73 m2 at baseline (HR, 4.49; 95% CI, 1.32-16.07; p = 0.017) were significantly associated with developing grade ≥2 proteinuria. These patients should be monitored carefully, and our preliminary data should be confirmed by further studies.

Prevalence Rate of Proteinuria and Metabolic Acidosis Among Kidney Transplant Recipients in a Tertiary Teaching Hospital and Its Relationship to Dietary Intake

Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake. We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records. A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n=163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m2 (IQR, 25 mL/min/1.73 m2). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P=.008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis. The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome.

POS-344 PREDICTIVE VALUE OF 25-HYDROXYVITAMIN D IN THE PROGRESSION OF DIABETIC NEPHROPATHY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Diabetic nephropathy occurs in about one-third of diabetic patients, and it manifests as increased urinary albumin excretion that eventually leads to decreased glomerular filtration rate and renal failure. Previous studies reported vitamin D deficiency as a possible risk factor for albuminuria and the development of diabetic nephropathy. In this study, we assessed the association between 25- hydroxyvitamin D (25OHD) serum level and albuminuria in patients with type 2 diabetes mellitus. In total, 200 patients with Type 2 diabetes were recruited from January to August 2021 and divided into three groups based on the urinary albumin-to-creatinine ratio (UACR); UACR < 30 mg/g was defined as normoalbuminuria, UACR levels of 30–300 mg/g and ≥ 300 mg/g were defined as microalbuminuria and macroalbuminuria, respectively. Vitamin D deficiency was described as a serum 25OHD level < 20 ng/ml. Serum 25OHD and other clinical characteristics among various UACR groups were compared. The relationship between albuminuria and 25OHD was analyzed. The patients with macroalbuminuria had significantly lower serum 25OHD levels and a higher prevalence of vitamin D deficiency than normal and microalbuminuric groups (all p-value <0.001). Also, there was a significant negative correlation between serum level of vitamin D and albuminuria state (r= -2965, P<0.0001). Logistic regression analyses demonstrated that vitamin D deficiency (25OHD < 20ng/ml) level were associated with macroalbuminuric state (odds ratio (OR) = OR=5.11, 95% CI= 2.23 to 11.73). ROC analysis indicated that a 25OHD level < 21 ng/ml suggested the occurrence of macroalbuminuria in diabetic patients. Vitamin D deficiency is an independent risk factor for diabetic nephropathy, and the prevalence of macroalbuminuria increased more than five folds when the 25OHD level is < 20ng/ml.

The role of vitamin D deficiency and elevated inflammatory biomarkers as risk factors for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus

Abstract Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Albuminuria is the most sensitive marker for the early recognition of DN. Therefore, we aimed to study the risk factors of albuminuria as a marker of DN among diabetic patients. The study included 41 patients with type 2 diabetes mellitus (T2DM), 50 type 2 diabetic nephropathy (T2DN) patients with macroalbuminuria, 43 T2DN patients with microalbuminuria and 38 healthy controls. Logistic regression was used to detect the most significant risk factors for albuminuria. A high statistically significant difference was found between the groups regarding age, sex, body mass index (BMI), diabetes mellitus (DM) duration, glucose, glycated haemoglobin (HbA1c), creatinine, glomerular filtration rate (GFR), lipid profile, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), the albumin–creatinine ratio (ACR), vitamin D, total parathyroid hormone (PTH), urea, total calcium and chemerin (p &lt; 0.001). It was found that the duration of DM, BMI, glucose, GFR, total cholesterol (TC), low-density lipoprotein (LDL), TNF-α, IL-6, CRP, ACR, vitamin D, PTH and chemerin are significant albuminuria risk factors in DN. Vitamin D deficiency and associated inflammatory mediators such as chemerin, TNF-α, IL-6 and CRP are the most essential risk factors for albuminuria in T2DM patients.

Risk factors associated with albuminuria in Rwanda: results from a STEPS survey

BackgroundNon-communicable diseases (NCDs) are a growing burden which affects every part of the world, including developing countries. Chronic kidney disease (CKD) has varied etiology which can result from or complicate other NCDs such as diabetes and cardiovascular diseases. The growing prevalence of NCDs coupled with the increasing age in most developing countries, has seen a marked increase of CKD in these settings. CKD has been described as “the most neglected NCD” and greatly affects the quality of life of patients. It also places a huge economic burden on societies. However, few epidemiological data exist, particularly in sub-Saharan Africa. Assessment of the prevalence of albuminuria as a marker of kidney damage and CKD progression and its main risk factors was thus needed in Rwanda.MethodsThis study analyzed data collected during the first STEPwise approach to NCD risk factor Surveillance (STEPS) survey in Rwanda, conducted from 2012 to 2013, to assess the prevalence of albuminuria. A multistage cluster sampling allowed to select a representative sample of the general population. Furthermore, descriptive, as well as univariable analyses and multiple logistic regression were performed to respond to the research question.ResultsThis survey brought a representative sample of 6,998 participants, among which 4,384 (62.65%) were female. Median age was 33 years (interquartile range, IQR 26-44), and over three quarters (78.45%) lived in rural areas. The albuminuria prevalence was 105.9 per 1,000 population. Overall, semi-urban and urban residency were associated with lower odds of CKD (odds ratio, OR 0.36, CI 0.23-0.56, p<0.001 and OR 0.34, CI 0.23-0.50, p<0.001, respectively) than rural status. Being married or living with a partner had higher odds (OR 1.44 (CI 1.03-2.02, p=0.031) and OR 1.62 (CI 1.06-2.48, p=0.026), respectively) of CKD than being single. Odds of positive albuminuria were also greater among participants living with human immunodeficiency virus (HIV) (OR 1.64, CI 1.09- 2.47, p=0.018). Gender, age group, smoking status and vegetable consumption, body mass index (BMI) and hypertension were not associated with albuminuria.ConclusionThe albuminuria prevalence was estimated at 105.9 per 1,000 in Rwanda. Rural residence, partnered status and HIV positivity were identified as main risk factors for albuminuria. Increased early screening of albuminuria to prevent CKD among high-risk groups, especially HIV patients, is therefore recommended.