Prospective urinary albumin/creatinine ratio for diagnosis, staging, and organ response assessment in renal AL amyloidosis: results from a large cohort of patients

Objectives Quantification of 24 h-proteinuria is the gold standard for diagnosing, staging, and monitoring of patients with renal AL amyloidosis. However, 24 h-urine collection is cumbersome and may result in preanalytical error. In this prospective study, we investigated the role of urinary albumin/creatinine ratio (UACR) (cut-off: 300 mg/g) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600 mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis. Methods From October 2013 paired 24 h-proteinuria and UACR (on first morning void) were measured in all newly-diagnosed patients with AL amyloidosis. Correlation between 24 h-proteinuria and UACR at baseline was assessed by Pearson’s r test. Impact of UACR response on renal outcome was assessed in randomly created testing (n=354) and validation (n=177) cohorts. Results A strong linear correlation was found between 24 h-proteinuria and UACR at baseline (r=0.90; p<0.001). After a median follow-up of 31 months, 57 (11%) patients required dialysis. A UACR-based renal staging system identified three stages with significantly higher dialysis rate at 36 months comparing stage I with stage II and stage II with stage III. Achieving a renal response, according to a UACR-based criterion, resulted in lower dialysis rate in both testing and validation cohorts. Conclusions UACR is a reliable marker for diagnosis, prognosis, and organ response assessment in renal AL amyloidosis and can reliably replace 24 h-proteinuria in clinical trials and individual patients’ management.

Exosomal and Plasma Non-Coding RNA Signature Associated with Urinary Albumin Excretion in Hypertension

Non-coding RNA (ncRNA), released into circulation or packaged into exosomes, plays important roles in many biological processes in the kidney. The purpose of the present study is to identify a common ncRNA signature associated with early renal damage and its related molecular pathways. Three individual libraries (plasma and urinary exosomes, and total plasma) were prepared from each hypertensive patient (with or without albuminuria) for ncRNA sequencing analysis. Next, an RNA-based transcriptional regulatory network was constructed. The three RNA biotypes with the greatest number of differentially expressed transcripts were long-ncRNA (lncRNA), microRNA (miRNA) and piwi-interacting RNA (piRNAs). We identified a common 24 ncRNA molecular signature related to hypertension-associated urinary albumin excretion, of which lncRNAs were the most representative. In addition, the transcriptional regulatory network showed five lncRNAs (LINC02614, BAALC-AS1, FAM230B, LOC100505824 and LINC01484) and the miR-301a-3p to play a significant role in network organization and targeting critical pathways regulating filtration barrier integrity and tubule reabsorption. Our study found an ncRNA profile associated with albuminuria, independent of biofluid origin (urine or plasma, circulating or in exosomes) that identifies a handful of potential targets, which may be utilized to study mechanisms of albuminuria and cardiovascular damage.

Chronic kidney disease biomarkers and mortality among older adults: A comparison study of survey samples in China and the United States

Objectives Among older adults in China and the US, we aimed to compare the biomarkers of chronic-kidney-diseases (CKD), factors associated with CKD, and the correlation between CKD and mortality. Setting China and the US. Study design Cross-sectional and prospective cohorts. Participants We included 2019 participants aged 65 and above from the Chinese Longitudinal Healthy Longevity Study (CLHLS) in 2012, and 2177 from US National Health and Nutrition Examination Survey (NHANES) in 2011–2014. Outcomes Urinary albumin, urinary creatinine, albumin creatinine ratio (ACR), serum creatinine, blood urea nitrogen, plasma albumin, uric acid, and estimated glomerular filtration rate (eGFR). CKD (ACR ≥ 30 mg/g or eGFR< 60 ml/min/1.73m2) and mortality. Analytical approach Logistic regression and Cox proportional hazard models. Covariates included age, sex, race, education, income, marital status, health condition, smoking and drinking status, physical activity and body mass index. Results Chinese participants had lower levels of urinary albumin, ACR, and uric acid than the US (mean: 25.0 vs 76.4 mg/L, 41.7 vs 85.0 mg/g, 292.9 vs 341.3 μmol/L). In the fully-adjusted model, CKD was associated with the risk of mortality only in the US group (hazard ratio [HR], 95% CI: 2.179, 1.561–3.041 in NHANES, 1.091, 0.940–1.266 in CLHLS). Compared to eGFR≥90, eGFR ranged 30–44 ml/min/1.73m2 was only associated with mortality in the US population (HR, 95% CI: 2.249, 1.141–4.430), but not in the Chinese population (HR, 95% CI: 1.408, 0.884–2.241). Conclusions The elderly participants in the US sample had worse CKD-related biomarker levels than in China sample, and the association between CKD and mortality was also stronger among the US older adults. This may be due to the biological differences, or co-morbid conditions.

Effect of multicomponent therapy on left ventricular diastolic function in resistant hypertension patients

The aim – to determine prognostic factors of improving left ventricular diastolic function (LV DF) in resistant hypertension (RH) patients (pts) treated with multicomponent antihypertensive therapy during three years.Materials and methods. 102 patients with true RH were included. Patients received triple fixed combination (blocker of the renin-angiotensin-aldosterone system / calcium antagonist / diuretic), to which has been added a fourth drug (spironolactone, eplerenone, moxonidine, torasemide or nebivolol). The state of LV DF was studied at the beginning and at the end of the study. Office and 24-h ambulatory blood pressure (BP) measurements, echocardiography, clinical characteristics, neurohumoral and proinflammatory status were assessed.Results and discussion. Impairment LV DF was detected in 75.5 % of pts. The first degree of LV diastolic dysfunction (DD) was observed in 63.7 %. The patients were divided into 2 groups: the first group included persons without initial impairment of LV DF (n=25), the second – pts with LV DD (n=77). Patients with LV DD were older, had a longer duration of hypertension, higher body mass index, 24-h urinary albumin excretion, office BP and 24-h ambulatory BP, more often (in 2 times) disorders of circadian BP rhythm and concomitant diabetes mellitus (DM). Left ventricular DD in 100 % of cases was associated with severe LV hypertrophy (LVH), increased plasma concentration of inflammatory proteins (CRP, fibrinogen), cytokines (IL-6, TNF-α), increased activity of leukocyte elastase, macrophage matrix metalloproteinase-12. The concentration in the blood of aldosterone, active renin, 24-h urinary excretion of metanephrines did not differ between the groups.Conclusions. Improvement and stabilization of LV DF occurred in parallel with regression of LVH (normalization of LVMI in 35.1 % of pts and significant decrease of LVMI in 64.9 %) against the background of decrease of BP and in the proportion of pts with disturbed circadian BP rhythm. The independent factors of the E/E’ ratio were the initial plasma concentrations of aldosterone (β=0.556; р=0.0001), glucose (β=0.366; р=0.0001), active renin (β=–0.223; р=0.004), 24-h urinary albumin excretion (β=0.188; р=0.016), age (β=0,192; р=0,023). The odds of an improvement in LV DF increased by 3.7 times, if the patient with RH had no DM, LVH regression occurred.

The relationship between urinary albumin to creatinine ratio and all-cause mortality in the elderly population in the Chinese community: a 10-year follow-up study

Background In patients with diabetes and hypertension, proteinuria is independently associated with all-cause death. However, in the general population, urinary albumin to creatinine ratio (UACR) is less used to predict all-cause mortality. When the urinary albumin to creatinine ratio is within the normal range (UACR< 30 mg/g), the clinical relevance of an increased urinary albumin excretion rate is still debated. We studied the relationship between UACR and all-cause mortality in community populations, and compared UACR groups within the normal range. Methods The participants were the inhabitants from the Wanshoulu community in Beijing, China. The average age is 71.48 years, and the proportion of women is 60.1%. A total of 2148 people completed random urine samples to determine the urinary albumin to creatinine ratio (UACR). The subjects were divided into three groups according to UACR: Group 1 (UACR< 10 mg/g), Group 2 (10 mg/g < UACR< 30 mg/g), Group 3 (UACR> 30 mg/g). We used Kaplan-Meier survival analysis and Cox regression model to verify the relationship between UACR and all-cause mortality. Results At an average follow-up of 9.87 years (718,407.3 years), the total mortality rate were 183.4/1000. In the Cox proportional hazards model, after adjusting for possible confounders, those with normal high-value UACR (group 2) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.289, 95% confidence interval (CI) 1.002 ~ 1.659 for all-cause mortality]. Those with proteinuria (group 3) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.394, 95% confidence interval (CI) 1.020 ~ 1.905 for all-cause mortality]. Conclusion Urinary albumin to creatinine ratio is an important risk factor for all-cause death in community population. Even if it is within the normal range (UACR< 30 mg/g), it occurs in people with high normal value (10 mg/g < UACR< 30 mg/g), the risk of all-cause death will also increase.

Differentiating glomerular from non-glomerular hematuria: role of urinary albumin-total protein ratio

Background: Hematuria is one of the most common and early signs of diseases related to genitourinary system and can be classified as either glomerular or non-glomerular in origin. Percentage of dysmorphic RBC (%dRBC) in urine has been in practice as a diagnostic tool for differentiating glomerular from non-glomerular hematuria. Recent studies indicate that, urinary albumin-total protein ratio (uAPR) can also be used as a diagnostic tool in this regard. This study aimed to evaluate the sensitivity and specificity of uAPR as a diagnostic tool for detecting glomerular hematuria in comparison to %dRBC in urine. Methods: This cross-sectional study enrolled 96 patients with hematuria. Fresh urine samples were collected from each subject to determine the %dRBC and to calculate uAPR. Receiver operating characteristic curve analysis was done on these results to evaluate the sensitivity and specificity of uAPR and %dRBC in differentiating glomerular from non-glomerular hematuria. Results: uAPR and %dRBC were significantly (p<0.001) higher among patients with glomerular hematuria than non-glomerular hematuria. At the cutoff value of 0.57 mg/mg, uAPR showed sensitivity of 81.8% and specificity of 95.5%. At the cutoff value of 22.5%, %dRBC showed sensitivity of 54.5% and specificity of 86.4%. Conclusion: uAPR has higher sensitivity and specificity than %dRBC in differentiating glomerular from nonglomerular hematuria and can be used as a diagnostic tool. BIRDEM Med J 2022; 12(1): 51-56

A Prospective Study of Urinary Albumin to Creatinine Ratio and Its Associated Causes

Urine albumin-to-creatinine ratio have predictive values for hypertension, diabetes mellitus, renal dysfunction etc. Albumin-to-creatinine ratio represents the severity of proteinuria, indicates high probability of damage to glomerular filtration capacity of the kidney and is of great diagnostic relevance. Emerging data suggested that reduction of albuminuria leads to reduced risk of adverse renal and cardiovascular events but also steps should be taken to suppress albuminuria to prevent future renal and cardiovascular adverse events. This review discusses the association between albuminuria and adverse cardiovascular and renal outcomes in type 2 diabetes and hypertension. This study aimed to review the association between normal ranges of urine albumin-to-creatinine ratio to cardiovascular and all-cause mortality.

Impact of Obesity in Kidney Diseases

The clinical consequences of obesity on the kidneys, with or without metabolic abnormalities, involve both renal function and structures. The mechanisms linking obesity and renal damage are well understood, including several effector mechanisms with interconnected pathways. Higher prevalence of urinary albumin excretion, sub-nephrotic syndrome, nephrolithiasis, increased risk of developing CKD, and progression to ESKD have been identified as being associated with obesity and having a relevant clinical impact. Moreover, renal replacement therapy and kidney transplantation are also influenced by obesity. Losing weight is key in limiting the impact that obesity produces on the kidneys by reducing albuminuria/proteinuria, declining rate of eGFR deterioration, delaying the development of CKD and ESKD, and improving the outcome of a renal transplant. Weight reduction may also contribute to appropriate control of cardiometabolic risk factors such as hypertension, metabolic syndrome, diabetes, and dyslipidemia which may be protective not only in renal damage but also cardiovascular disease. Lifestyle changes, some drugs, and bariatric surgery have demonstrated the benefits.

Protective Effect of Adalimumab on Diabetic Nephropathy by Regulating TNF-α Signal Pathway

Background: To evaluate the inhibitory effect of adalimumab on diabetic nephropathyDN) through animal models. Methods: We carried out the study in Weifang People’s Hospital, Weifang 261041, China in December 2020. Streptozotocin was used to induce DN in model animal Sprague-Dawley (SD) rats. The DN animal model was given treatment with adalimumab, and the inhibitory effect of adalimumab on the development process of DN was evaluated by detecting changes in blood glucose and urinary albumin levels. Meanwhile, the content of UN, Cr and CysC of the blood in different experimental groups was tested by weighing the ratio of kidney and performing ELISA to evaluate the protective effect of adalimumab on kidney of DN animal model. In addition, the changes in the transcription and translation levels of tumor necrosis factor α (TNF-α) and its downstream regulatory factors MCP-1 and NF-kB in kidney of different experimental groups were detected by fluorescence quantitative PCR and Western blot tests to further reveal the molecular mechanism of adalimumab inhibiting the diabetic nephropathy. Results: adalimumab could significantly downregulate blood glucose and urinary albumin levels (P <0.05). The renal body weight ratio and the contents of UN, Cr and Cysc in blood in the adalimumab group were significantly lower than those in the placebo group (P <0.05). Meanwhile, adalimumab could significantly downregulate the expression of these molecules (P <0.05). Conclusion: adalimumab could exert its therapeutic effect on diabetic nephropathy through its specific targeting TNF-α signaling pathways.

Influence of Polyunsaturated Fatty Acid Intake on Kidney Functions of Rats with Chronic Renal Failure

Arachidonic acid (ARA), an omega-6 (ω-6) polyunsaturated fatty acid (PUFA), is involved in the development and maintenance of renal functions, whereas docosahexaenoic acid (DHA) is an omega-3 (ω-3) PUFA that has anti-inflammatory effects and attenuates nephropathy. However, their effects on the progression of chronic kidney disease (CKD) remain unknown. The aim of this study was to assess the effects of feeding ARA, DHA, and ARA and DHA-containing diets on rats with 5/6 nephrectomized kidneys. Urine and feces were collected every 4 weeks, and the kidneys were collected at 16 weeks after surgery. Urinary albumin (U-ALB) excretion increased gradually with nephrectomy, but the U-ALB excretion was attenuated by feeding the rats with an ARA + DHA-containing diet. Reactive oxygen species (ROS) levels in the kidneys were lower in the ARA + DHA group than in the other groups. At 4 weeks after surgery, the lipid peroxide (LPO) levels in the plasma of the ARA + DHA groups decreased significantly after surgery compared to the control CKD group, but this did not happen at 16 weeks post-surgery. There was a significant negative correlation between LPO levels in the plasma at 4 weeks and creatinine clearance, and a positive correlation with urinary albumin levels. These results suggest that the combination of ARA and DHA inhibit the progress of early stage CKD.