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.

The Effect of Diabetes and the Diabetogenic TBC1D4 p.Arg684Ter Variant on Kidney Function in Inuit in Greenland

ObjectiveDiabetes prevalence in Greenland is high and increasing. The aim of this study was to examine the effect of diabetes and the diabetogenic TBC1D4 variant on kidney function in Greenland in a population-based setting.Research Design and MethodsHealth survey data and TBC1D4 genotypes from 5,336 Greenlanders was used to estimate odds ratios (ORs) of albuminuria (>30 mg/g creatinine) and chronic kidney disease (CKD, eGFR<60 ml/min/1.73m2), comparing individuals with and without diabetes. Using baseline and follow-up data from individuals who participated in two surveys we examined the effect of diabetes on eGFR and urinary albumin creatinine ratio (UACR) at follow-up, stepwise adjusting for baseline confounders including the TBC1D4 variant.ResultsA total of 9.3% had diabetes of the 3,909 participants with complete data. Albuminuria and CKD was found in 27.6% and 9.5% among those with and without diabetes respectively. Diabetes was associated with increased risk of albuminuria (OR(95% CI) = 2.37 (1.69,3.33) p<0.001) and the TBC1D4 variant protected against albuminuria (OR(95% CI) = 0.44 (0.22,0.90) p=0.02) in a multivariable model. Neither diabetes nor the TBC1D4 variant significantly associated with CKD. Diabetes was not associated with changes in eGFR or UACR over a median of 11.3 years.ConclusionDiabetes conferred increased risk of albuminuria and the TBC1D4 variant was associated with decreased risk of albuminuria, but neither were associated with CKD. The presence/absence of diabetes did not predict changes in eGFR and UACR in longitudinal analyses. The potential renoprotective association of the TBC1D4 variant on albuminuria calls for further studies.

Early Vascular Aging in Children With Type 1 Diabetes and Ambulatory Normotension

Background: Preliminary data suggest that target organ damage (TOD) and early vascular aging (EVA) may occur in children with normal blood pressure (BP).Objectives: To analyze TOD and EVA in normotensive (BP &lt;95th percentile on ambulatory BP monitoring) type 1 diabetes children (T1D) in comparison to healthy controls (C).Subjects: 25 T1D aged 13.9 ± 2.6 years and 22 C aged 14.0 ± 3.4 years.Methods: We analyzed age- and height-related pulse wave velocity (PWV) Z-scores and expected PWV based on age, height, and mean arterial pressure (MAP). Expected vascular age based on measured PWV was calculated from pooled pediatric and adult PWV norms. Left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (ACR) were obtained as markers of TOD.Results: T1D and C groups did not differ in anthropometry, ambulatory, LVMI, and ACR. However, median age- and height-related PWV Z-scores were higher in T1D compared to C (1.08 vs. 0.57, p = 0.006; 0.78 vs. 0.36, p = 0.02, respectively). Mean (±SD) difference between measured and expected PWV was 0.58 ± 0.57 in T1D vs. 0.22 ± 0.59 in C, p = 0.02. The mean (±SD) difference between chronological and expected vascular age was 7.53 ± 7.74 years in T1D vs. 2.78 ± 7.01 years in C, p = 0.04.Conclusion: Increased arterial stiffness and increased intraindividual differences between expected and measured PWV as well as between chronological and expected vascular age indicate that EVA may develop in T1D children even at normal ambulatory BP levels.

Machine Learning for Screening Microvascular Complications in Type-2 Diabetic Patients using Demographic, Clinical, and Laboratory Profiles

Microvascular complications are one of the key causes of mortality among type-2 diabetic patients. This study was sought to investigate the use of a novel machine learning approach for predicting these complications from patient demographic, clinical, and laboratory profiles only. A total of 96 Bangladeshi participants having type-2 diabetes were recruited during their routine hospital visits. All patient profiles were assessed by using a Chi-squared (2) test to statistically determine the most important markers in predicting four microvascular complications; namely cardiac autonomic neuropathy (CAN), diabetic peripheral neuropathy (DPN), diabetic nephropathy (NEP), and diabetic retinopathy (RET). A machine learning approach based on random forest (RF) and support vector machine (SVM) was then developed to ensure automated clinical testing for microvascular complication in diabetic patients. The highest prediction accuracies were obtained by RF using diastolic blood pressure, Albumin-Creatinine ratio, and gender for CAN testing (98.67%), Microalbuminuria, smoking history, and hemoglobin A1C for DPN testing (67.78%), Albumin-Creatinine ratio for NEP testing (100%), and hemoglobin A1C, Microalbuminuria, and smoking history for RET testing (84.38%). This study suggests machine learning as a promising automated tool for predicting microvascular complications in diabetic patients using their profiles, which could help prvent those patients from further microvascular complications leading to early death.

Renal Acoustic Radiation Force Impulse Elastography in Hypertensive Nephroangiosclerosis Patients

Objective: Hypertensive nephroangiosclerosis (HN) represents the second most common cause of chronic kidney disease. Kidney damage secondary to high blood pressure favors the appearance of serum and urinary changes, but also imaging, highlighted by ultrasonography (B-mode, Doppler, Acoustic Radiation Force Impulse Elastography). Acoustic Radiation Force Impulse Elastography (ARFI) represents a new imagistic method which characterizes renal stiffness in the form of shear wave velocity (SWV). Aim: This study aims to investigate renal stiffness in HN patients, and to assess the correlations between it and urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and intrarenal resistive index (RRI). Material and Methods: This cross-sectional study was performed on a group of 80 HN patients and 50 healthy, sex and age-matched, as controls. UACR (urinary immunoturbidimetry), eGFR (Jaffe method), RRI, and renal SWV (Siemens Acuson 2000) were determined in all patients and controls. Data were expressed as mean ± standard deviation. Statistical analysis was done by means Pearson’s test and t-Student test, p values of less than 0.05 were considered statistically significant. Results: UACR, eGFR, RRI and SWV showed statistically significant differences between the HN patients and controls (p < 0.0001). In the hypertensive patients group, statistically significant correlations were observed between the SWV and UACR (r = −0.7633, p < 0.00001), eGFR (r = 0.7822, p = 0.00001), and RRI (r = −0.7978, p = 0.00001). Conclusions: Kidney sonoelastography characterizes imagistically the existence of intrarenal lesions associated with essential hypertension, offering a new diagnosis method for these patients.

Correlation of Pentosidine with Kidney Diseases in Iraqi Patients with Diabetic Nephropathy

Diabetic nephropathy (DN) is a principle cause of microangiopathy and the main reason for kidney disease at the end stage in patients with type 2 diabetes mellitus (T2DM). This work aimed to study the relation of pentosidine with kidney injury in the case of diabetic nephropathy. This study included 75 patients suffering from T2DM and 75 apparently healthy subjects. The patients group was divided into three groups ((normoalbumin, microalbuminuria, and macroalbuminuria; 25 patients for each) on the basis of albumin-creatinine ratio (ACR) . The level of serum pentosidine was determined using an ELISA kit. The level of pentosidine was found to be significantly higher in DN patients than in the healthy group. Also, the results revealed a strong positive correlation of pentosidine with each of creatinine and blood urea levels, while a negative correlation was recorded with eGFR. It can be concluded that pentosidine may be associated with disease progression and it may be employed as one of the most efficient markers for the prediction of renal function.

Risk factors for development of nephropathy in patients with a diabetic Charcot foot

Objective Charcot foot is a rare complication to neuropathy and can cause severe foot deformities and ulcerations, which often require prolonged antibiotical treatment. The objective of this retrospective study was to investigate whether this treatment is associated to impaired renal function. Results In total, 163 patients were included, of whom 105 (64%) had received β-lactam antibiotics for a mean total duration of 13.0 months. There was a significant increase in the urine albumin/creatinine ratio in the group that received antibiotics (p = 0.017), and the use of antibiotics was associated to a subsequent diagnosis of nephropathy (p = 0.01). Patients treated with antibiotics had a 21.9% risk of developing subsequent nephropathy versus 5.2% for patients not treated with antibiotics. We suggest increased awareness on signs of nephropathy in patients with severe Charcot foot.

Fibrosis biomarkers and echocardiographic parameters in patients with type 2 diabetes depending on the degree of albuminuria

Background. Diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM) is associated with a risk of developing chronic heart failure (CHF). The degree of albuminuria is a marker of DN and is associated with an increased risk of chronic heart failure (CHF).Aim. To evaluate fibrosis biomarkers and echocardiographic parameters in patients with T2DM without CHF, depending on urinary albumin excretion.Materials and methods. The study included 42 patients with T2DM without verified CHF. The patients were divided into two groups: 1) a group with normoalbuminuria and 2) a group with a moderate increase in albuminuria (albumin / creatinine ratio of 30–300 mg / g). Echocardiography was performed and galectin-3, ST-2, PIСP, MMP-9, and TIMP-1 concentrations were measured.Results. The groups did not differ by age, sex, body mass index (BMI), glycated hemoglobin (HbA1c), and glomerular filtration rate (GFR). Galectin-3 concentrations were significantly higher in the group with a moderate increase in albuminuria than in the group of patients without albuminuria – 13.6 (11.2; 15.1) ng / ml and 7.4 (6.7; 7.9) ng / ml, respectively, p = 0.002. The groups also did not differ in the values of biomarkers, such as P1CP, TIMP-1, and MMP-9. Besides, the group with normoalbuminuria had lower E/e’ values than the group with a moderate increase in albuminuria – 8 (7; 9) and 10 (9; 12.5), p = 0.02.Conclusion. The patients with type 2 diabetes and a moderate increase in albuminuria have higher values of galectin-3 and a more pronounced diastolic dysfunction. The identified changes may reflect a higher risk of chronic heart failure in this group of patients.

ALBUMIN CREATININE RATIO AS AN INDICATOR OF NON-HEALING FOOT WOUND FORMATION IN DIABETES

Aims: To investigate whether kidney injury, determined by albumin creatinine ratio, was associated with current non-healing foot wounds in type 2 diabetes. Materials and Methods: Eighty–nine Barbadians with diabetes were recruited. Cases had a current foot wound and controls had no current foot wound and no history of a non-healing foot wound. Cases were matched to controls using sex, age and duration of diabetes. Participants were from wound dressing and diabetes clinics at the Queen Elizabeth Hospital and Polyclinics, and from private healthcare practitioners. The relationship between albumin creatinine ratio and foot ulceration, adjusting for selected potential risk factors, was analyzed using logistic regression and presented as odds ratios. Results: Forty–four cases and 45 controls were matched, with no statistically significant difference in matching criteria. There were statistically important differences in measures of neuropathy, blood glucose, HbA1c and Albumin:creatinine ratio between cases and controls. Cases were 3 times more likely than controls to have microalbuminuria (95% CI 0.9 – 10.2; p=0.08). Cases were 7.4 times more likely than controls to have macroalbuminuria (95% CI 1.2 – 47.5; p=0.04). Conclusions: The possible association of albumin:creatinine ratio with diabetic foot wounds raises the possibility of its use in earlier identification of persons on the pathway to developing diabetic foot.