Clinical Proteinuria Research Articles

Relationship between serum level of miR-338-3p and miR-105-3p and bone metabolic markers in patients with diabetes nephropathy

Objectives Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes. The purpose of this study was to explore the relationship between serum microRNA-338-3p (miR-338-3p) and miR-105-3p and bone metabolic markers in patients with DN at different stages. Methods A total of 153 patients diagnosed and treated in the Department of Nephrology from July 2020 to October 2021 were selected as the study objects. According to the staging criteria of diabetic nephropathy and 24-h urinary albumin quantitative level, the patients were divided into control group (35 cases), microalbuminuria group (37 cases), clinical stage albuminuria group (27 cases) and renal failure group (54 cases). Gene expressions were measured by real-time fluorescence quantitative PCR. The correlation was analyzed by Spearman. Serum miR-338-3p and miR-150-5p in the prediction of renal failure in DN was analyzed by ROC curve. Results The levels of urinary albumin and serum creatinine were markedly increased with the increase of DN stage (p < 0.05). Compared with the microalbuminuria group, the expression levels of serum miR-383-3p, serum miR-105-3p, 25(OH)-D, BGP and PINP were obviously decreased, but the expression of parathyroid hormone (PTH) and type I collagen (β-CTX) was largely increased in clinical proteinuria group (p < 0.05). Compared with the clinical proteinuria group, the expression levels of serum miR-383-3p, serum miR-105-3p, 25(OH)-D, BGP and PINP were largely decreased, but the expression of PTH and β-CTX was obviously increased in the renal failure group (p < 0.05). Spearman correlation results showed that serum expressions of miR-383-3p and miR-105-3p were negatively correlated with PTH and β-CTX, and positively correlated with 25(OH)-D, BGP and PINP (p < 0.05). ROC curve analysis showed that the AUC of serum miR-338-3p and miR-150-5p was 0.896 with the specificity and sensitivity of 96.66% and 73.47%, which had certain predictive value for the occurrence of renal failure in DN. Conclusions The expression levels of serum miR-383-3p and miR-105-3p were significantly correlated with bone metabolism markers. The combined test can provide new ideas and insights for the clinical treatment of osteoporosis in DN.

Adverse Events in Targeted Therapy for Unresectable Hepatocellular Carcinoma Predict Clinical Outcomes.

To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532-1.450-2.361 (p for trend 0.037), 1.057-1.691-3.364 (p for trend 0.004), 1.176-0.686-0.281 (p for trend 0.002), 0.639-0.759-1.820 (p for trend 0.462), 1.030-0.959-0.147 (p for trend 0.011), and 0.697-0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592-1.073-2.811 (p for trend 0.255), 1.161-1.282-4.324 (p for trend 0.03), 0.965-0.781-0.655 (p for trend 0.095), 0.737-0.623-2.147 (p for trend 0.153), 1.061-0.832-0.800 (p for trend 0.391), and 1.412-0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects.

Partial long-term clinical improvement after a BCG challenge in systemic lupus erythematosus-prone mice

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus’s autoimmune response.

High prevalence of albuminuria among adult males living with HIV in Botswana

Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among people living with HIV (PLWH) in sub-Saharan Africa. Therefore, we conducted a cross-sectional observational HIV clinic-based study of albuminuria among 1533 adults aged 21 years or older between January 2020 and January 2021 in Gaborone, Botswana. Clinical albuminuria was defined using a sex-based albumin‒creatinine ratio (ACR) of 25–355 mg/g for females and 17–250 mg/g for males. The study population mean age was 48.5 (SD 10.3) years, and 764/1533 (49.7%) were female. The overall prevalence of albuminuria was 20.7% (95% CI 18.7%, 22.8%). A higher proportion of males were more likely to be categorized as having albuminuria than females, 25% (95% CI 22.0, 28.2) versus 16.4% (95% CI 13.8,19.2), P value < 0.001. In the final multivariate models, predictors of albuminuria differed by sex group. Larger longitudinal studies are required to evaluate the impact of albuminuria among PLWH with particular emphasis on the effect of sex on the risk of albuminuria.

Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1

Introduction: The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remain uncertain, warranting further research. Methods: A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS + immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups. Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS + immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-h proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 mL/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable. Conclusion: Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.

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

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

Correlation between serum IL-22 and IL-27 levels and vasculopathy in diabetic nephropathy patients.

To explore the correlation between serum interleukin-22 (IL-22) and interleukin-27 (IL-27) levels and vasculopathy in patients with diabetic nephropathy (DN). A total of 104 DN patients treated at the Shanxi University of Traditional Chinese Medicine Affiliated Hospital were selected as the observation group, with another 104 healthy individuals, serving as the control group in this retrospective study. The baseline data and the serum levels of IL-22 and IL-27 were compared between the two groups. The observation group was divided into three subgroups based on their urinary albumin excretion rate (UAER): clinical albuminuria group (microangiopathy, 29 patients), microalbuminuria group (51 patients), and normal albuminuria group (24 patients). Logistic regression was used to analyze the factors influencing the occurrence of microangiopathy. According to whether they had major adverse cardiovascular events (MACE) during 6-month follow-up, the DN patients were divided into a MACE group (n = 39) and a non-MACE group (n = 65). The serum levels of IL-22 and IL-27 were then compared between the two groups. The clinical utility of IL-22 and IL-27 in the assessment of microangiopathy and prognosis was evaluated through receiver operating characteristic (ROC) curve analysis. Compared to the control group, the observation group exhibited significantly higher serum levels of fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein, uric acid, blood creatinine, cystatin C, IL-22 and IL-27, but lower glomerular filtration rate (all P<0.05). There were significant differences among different albuminuria groups in terms of duration of disease, serum levels of fasting blood glucose, low-density lipoprotein, cystatin C, IL-22, IL-27, and glomerular filtration rate (all P<0.05). Correlation analysis showed that the serum levels of IL-22 and IL-27 were positively correlated with the duration of disease and serum levels of fasting blood glucose, low-density lipoprotein, uric acid, blood creatinine and cystatin C. However, they were negatively correlated with glomerular filtration rate (P<0.05). The logistic regression analysis indicated that the glomerular filtration rate and serum levels of cystatin C, IL-22, and IL-27 were independent risk factors for the occurrence of microangiopathy. Compared to non-MACE group, the MACE group presented with higher serum IL-22 and IL-27 levels. ROC curve analysis showed that the AUC (Area Under the Curve) for combined detection (>0.9) of serum IL-22 and IL-27 levels was higher than that (>0.8) for each alone in assessing microangiopathy in DN patients. Additionally, the AUC for using serum IL-22 and IL-27 levels, whether individually or in combination, exceeded 0.7 when evaluating patient prognosis. Elevated serum IL-22 and IL-27 levels are closely associated with the severity of the DN and can serve as auxiliary indicators for assessing microangiopathy and prognosis in DN patients.

Ferroptosis: an important player in the inflammatory response in diabetic nephropathy.

Diabetic nephropathy (DN) is a chronic inflammatory disease that affects millions of diabetic patients worldwide. The key to treating of DN is early diagnosis and prevention. Once the patient enters the clinical proteinuria stage, renal damage is difficult to reverse. Therefore, developing early treatment methods is critical. DN pathogenesis results from various factors, among which the immune response and inflammation play major roles. Ferroptosis is a newly discovered type of programmed cell death characterized by iron-dependent lipid peroxidation and excessive ROS production. Recent studies have demonstrated that inflammation activation is closely related to the occurrence and development of ferroptosis. Moreover, hyperglycemia induces iron overload, lipid peroxidation, oxidative stress, inflammation, and renal fibrosis, all of which are related to DN pathogenesis, indicating that ferroptosis plays a key role in the development of DN. Therefore, this review focuses on the regulatory mechanisms of ferroptosis, and the mutual regulatory processes involved in the occurrence and development of DN and inflammation. By discussing and analyzing the relationship between ferroptosis and inflammation in the occurrence and development of DN, we can deepen our understanding of DN pathogenesis and develop new therapeutics targeting ferroptosis or inflammation-related regulatory mechanisms for patients with DN.

An audit of a general practices compliance with national recommendations for the avoidance of complications for type 2 diabetic patients

Abstract Introduction Each week, diabetes leads to more than 700 strokes, almost 600 heart attacks and more than 2000 instances of heart failure, in addition to being the single most common cause of chronic kidney disease in the UK.1 The NHS spends 10% of its annual budget on diabetes with 80% of that treating the complications of diabetes.2 Pharmacists have a crucial role to optimise the medication of diabetic patients and prevent future problems. Aim To assess a general practices (GP) compliance with national recommendations and the Quality and Outcomes Framework for the avoidance of complications for Type 2 Diabetes Mellitus (T2DM) patients. Methods This single-centre, retrospective audit was conducted at a GP in the London Borough of Southwark. Six standards were measured focusing on the prevention of the complications of diabetes. Each standard incorporated an exclusion and inclusion criteria. Standard 1 and 2 reviewed the appropriate management of nephropathy and hypertension respectively. Standard 3 and 4 relate to statin use for primary and secondary prevention. The final standards assess how many patients have documented QRISK2 scores and initiated on a Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitor as per the new NICE guidelines.3 Ethical approval was not deemed necessary for this clinical audit in agreement with the Hurley Group and King’s College Hospital NHS Foundation Trust guidelines. Results Half (50%, n=153/304) of all included T2DM patients at the practice have a blood pressure reading defined as hypertensive. Out of all diabetic patients, 25 of them had clinical proteinuria, micro-albuminuria, or a diagnosis of nephropathy. Of these 25 patients, 19 (76%) were prescribed an angiotensin-converting enzyme inhibitor or angiotensin-receptor blockers. A small portion (7%, n=28/374) of the diagnosed T2DM patients have a documented QRISK2 score. Subsequently, only 32 diabetic patients (9%, n=32/374) are prescribed an SGLT2 inhibitor. For standards 3 and 4, there were 122 patients (73%) who were prescribed a statin for primary prevention and 89 patients (87%) who were prescribed a statin for secondary prevention. Discussion/Conclusion The microvascular and macrovascular complications of diabetes are well documented. The incidence of these complications can be reduced by pharmacological management. Although none of the standards were met, the results are similar to other practices across the country. However, in comparison to the local average, the audited GP underperformed with no standards being better than the average of GPs in the area. Sub-analysis emphasises the disparities in health between various racial and ethnic groups. The results of the two largest demographic groups audited, Caucasian and Caribbean patients, show that the former is more likely to meet the standards. These findings indicate that the processes of the practice require change to meet the needs of our diabetic patients. In particular, work is required to understand the disparities in care for our patients categorised as ethnic minorities. The recommendations fall under 5 main categories – feedback, learn, templates, analyse, and review.

Further understanding and paying attention to normoalbuminuric diabetic kidney disease

Diabetes mellitus (DM) has grown up to be an important issue of global public health because of its high incidence rate. Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease (ESKD). Therefore, early diagnosis and timely prevention and treatment of DKD are essential for the progress of DM. The clinical diagnosis and staging of DKD are mostly based on the urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR). However, clinically, DKD patients show normoalbuminuric diabetic kidney disease (NADKD) instead of clinical proteinuria. The old NADKD concept is no longer suitable and should be updated accordingly with the redefinition of normal proteinuria by NKF/FDA (National Kidney Foundation/Food and Drug Administration). Based on the relevant guidelines of DM and chronic kidney disease (CKD) and combined with the current situation of clinical research, the review described NADKD from the aspects of epidemiology, pathological mechanism, disease diagnosis, clinical characteristics and biomarkers, to arouse the new understanding of NADKD in the medical profession and pay attention to it.

Daño renal oculto en pacientes diabéticos.

Introduction: Up to 40% of patients with type 2 Diabetes mellitus (T2DM) develop diabetic nephropathy (DN). This variable proportion depends on several intrinsic factors of the population. The study's objective was to describe the renal functional stage of patients with T2DM and to demonstrate the incidence of occult kidney damage in patients admitted to a provincial reference center for patients with T2DM in Holguín, Cuba. Methods: The present observational, cross-sectional, and prospective study was conducted at the Provincial Diabetic Center in Holguín from March 2019 to March 2021. Cases of patients with T2DM were included. The variables were demographic and clinical (Albuminuria, hyperglycemia, hypertension, proteinuria, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and fundus). The sample was probabilistic, consisting of 377 cases. Descriptive statistics were used. Results: 537 patients with T2DM were analyzed, including 341 women (63.5%). Patients &gt; 60 years old were 259 (48.2%). The time of diagnosis of T2DM was &lt;1 year in 270 cases (50.3%). 74 cases (13.8%) were patients with already established DN. Patients with obesity and overweight were 74.9%. The presence of albuminuria in grades A2 and A3 was 21.2% (CI95 17.8-24.7%). 60% of cases presented hypertriglyceridemia. High blood pressure occurred in 75.6%. In 79 cases (14.7%), there was diabetic retinopathy. CKD-EPI stage 2 had 254 cases, or 47.3%. Conclusion: Most patients with T2DM (82.1%) have chronic kidney disease in stages 2 to 5. Over half (60%) present Hypertriglyceridemia, obesity, and high blood pressure.

#5662 PRELIMINARY RESULTS FROM IBEAT ANCILLARY-STUDY: A NOVEL CLASSIFICATION OF RENAL DAMAGE IN DIABETES

Abstract Background and Aims Renal damage in diabetes can manifest as real diabetic glomerulosclerosis (DN) or non-diabetic renal disease (NDRD). DN and NDRD differ in terms of prognosis and treatment thus kidney biopsy remains the gold standard. The iBEAt study conducted within the frame of IMI project BEAt-DKD (https://www.beat-dkd.eu/; GA No 115974) aims to determine whether renal imaging biomarkers capture by magnetic resonance (MRI) and ultrasound (US) can dissect DKD heterogeneity. This ancillary sub-study in iBEAt aims to explore correlations between imaging biomarkers, clinical, molecular and renal histopathological data, in order to identify different DKD phenotypes. Method Up to January 2023 we enrolled 69 patients with: ages18-80; diagnosis of type 2 diabetes; eGFR &amp;gt; = 15 ml/min/1.73m2. Patients underwent kidney biopsy, US and MRI, along with biofluids and clinical data collection. For each patient, a total of three renal cores were collected, one was fixed in formalin, embedded in paraffin and used for routine diagnostics, the other was split and either included in OCT or used for electron microscopy, while the last was stored in RNA later for omics analysis. Results Among the 69 patients enrolled, 57 underwent kidney biopsy and US, with 47 also undergoing MRI. According to the KDIGO guidelines our cohort included: 12 A1 stage patients (1 G1, 1 G2, 2 G3a, 6 G3b, 2 G4); 27 in A2 stage (7 G1, 7 G2, 4 G3a, 7 G3b, 2 G4) and 21 in A3 (2 G1, 6 G3a, 6 G3b, 7 G4). According to the histological classification by Mazzucco et al (Am J Kidney Disease, 2002), 31% of DKD patients were categorized as Class 1 (diabetic glomerulosclerosis); 33% as Class 2 (vascular and ischemic glomerular changes); 4% as Class 3a (glomerular diseases superimposed on DN); 31% as Class 3b (other glomerulonephritis in the absence of DN). Pathologists assessment evidenced the presence of heterogeneous lesions among patients included within the same Mazzucco class. We thus proposed a novel classification of DKD, based both on renal pathology and according to the pathogenetic drivers. We identified 7 different histological classes of DKD: i) Class I: pure DN; ii) Class II: DN and nephroangiosclerosis; iii) Class III: DN and acute tubular necrosis; iv) Class IV: DN and Focal Segmental Glomerulosclerosis (FSGS); v) Class V: Nephroangiosclerosis; vi) Class VI: FSGS and other GN; vii) Class VII: FSGS and nephroangiosclerosis. According to the pathogenic drivers of DKD, we then grouped these classes in: pure metabolic damage (class I), metabolic damage and other drivers (including classes II, III, IV), pure vascular damage (class V) and immunological damage (classes VI, VII). Applying the newly proposed classification, we observed a significantly different distribution of key clinical parameters, uACR (p = 0.02), eGFR (p = 0.012), serum creatinine (p = 0.002) and proteinuria (p = 0.004). PAS glomerular staining positivity confirmed the more severe glomerular damage in the metabolic classes (p = 0.02); the wall-to-lumen ratio was able to significantly discriminate patients with vascular from those with immunological damage (p = 0.002). Finally, the renal resistive index measured through US significantly discriminated pure DN from mixed forms (p = 0.02) Conclusion The classification of renal damage in diabetes could represent a key strategy in the stratification of patients for precision medicine. The integration of renal pathology, US, ongoing MRI and omics data from the same patient has the potential to unlock new diagnostic tools and criteria to more accurately define the variety of renal phenotypes in diabetes.

#5514 IGA NEPHROPATHY: A REAL-WORLD COMPARISON BETWEEN DISEASE SEVERITY, SYMPTOM BURDEN, AND TREATMENT SATISFACTION REPORTED BY PATIENTS AND NEPHROLOGISTS

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, with an estimated annual incidence of ∼25/1000000. IgAN presents with many clinical manifestations, including hematuria, proteinuria, and hypertension (high blood pressure). This analysis aims to compare perceptions of symptom burden, disease severity and treatment satisfaction between patients living with IgAN and their treating nephrologists in Europe, the United States (US) and Asia. Method Data were drawn from the Adelphi IgAN Disease Specific Programme, a point-in-time survey of IgAN-treating nephrologists and their consulting IgAN patients, conducted in the US, Europe (EU5; France, Germany, Italy, Spain, United Kingdom [UK]), Japan, and China, June-October 2021. Nephrologists completed structured online patient record forms for successive patients presenting with IgAN. Patients voluntarily completed questionnaires that corresponded with the nephrologist records. Both the nephrologist and patient-reported data included demographics, IgAN signs and symptoms, disease severity and treatment satisfaction. Results Data was collected for 991 patients with IgAN, where matched nephrologist and patient- reported forms were completed. Mean (standard deviation [SD]) patient age was 42.1 (13.8) years, and 57% were male. Nephrologists and patients reported their perceived severity of the patient's IgAN, on a scale of mild, moderate, and severe (n = 981). Nephrologists and patients agreed on severity for 77% of patients (US 82%, EU5 77%, Japan 70%, China 78%). The level of nephrologist awareness of patient-reported symptoms was analysed. Where patients reported nausea/vomiting, it was not recognised by nephrologists in 85% of cases. This was similarly seen for appetite loss (80%), headaches/migraines (69%), and aching joints (67%). Patients and nephrologists were asked to score the patient's fatigue and pain on a scale from 0 (none) to 10 (worst possible). Overall, nephrologists and patients agreed on the patient's fatigue score in 33% of cases (n = 991). Fatigue was under-reported by nephrologists in comparison to what patients reported in 46% of cases with a mean (SD) difference in score of 2.47 (1.46), and over-reported in 21% of cases with a mean (SD) score difference of 1.95 (1.27). Patients and nephrologists agreed on the patient's self-reported pain score in 53% of cases (n = 988). Pain was under-reported by nephrologists in 26% of cases with a mean (SD) score difference of 2.24 (1.44) and over-reported in 21% of cases with a mean (SD) 2.06 (1.48) score difference. Nephrologists and patients reported their satisfaction with the patients’ current IgAN treatment as satisfied, neither satisfied or dissatisfied, or dissatisfied (n = 982). There was a 65% agreement between the nephrologists and patients’ treatment satisfaction. Percentage agreement varied across countries: EU5 76%, US 77%, China 61%, Japan 58%. Conclusion Although there seemed to be a good level of agreement between nephrologists and patients on their overall IgAN severity, nephrologists under-reported patient symptoms, notably nausea/vomiting and appetite loss, and fatigue. Although not IgAN specific, these symptoms can decrease a patient's quality of life. Satisfaction with current treatment also differed in around a third of cases. This highlights that communication between nephrologists and their patients can be improved, especially when it comes to appreciating IgAN symptom burden. This could be combated through more investment in a holistic patient evaluation. Cultural differences may impact symptom perception and reporting, as evidenced by differences between nephrologists and patients in different countries/regions. An improvement in communication may lead to a better management of IgAN patients, including treatment, and subsequently a better quality of life for patients with IgAN.

Diagnostic and prognostic performance of renal compartment volume and the apparent diffusion coefficient obtained from magnetic resonance imaging in mild, moderate and severe diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). There are unmet needs for noninvasive diagnosis and prognosis prediction of DKD in clinical practice. This study examines the diagnostic and prognostic value of magnetic resonance (MR) markers of renal compartment volume and the apparent diffusion coefficient (ADC) for mild, moderate, and severe DKD. This study was registered at the Chinese Clinical Trial Registry Center (registration number: ChiCTR-RRC-17012687). Sixty-seven DKD patients were prospectively randomly enrolled and underwent clinical examination and diffusion-weighted magnetic resonance imaging (DW-MRI). Patients with comorbidities that affected renal volumes or components were excluded. Ultimately, 52 DKD patients were included in the cross-sectional analysis. The ADC in the renal cortex (ADCcortex), ADC in the renal medulla (ADCmedulla) and difference between ADCcortex and ADCmedulla (ΔADC) were measured using a twelve-layer concentric objects (TLCO) approach. Renal compartment volumes of the parenchyma and pelvis were derived from T2-weighted MRI. Due to lost contact or ESRD diagnosed before follow-up (n=14), only 38 DKD patients remained for follow-up (median period =8.25 years) to investigate the correlations between MR markers and renal outcomes. The primary outcomes were the composite of doubling of the primary serum creatinine concentration or ESRD. ADCcortex presented superior performance in discriminating DKD with normal and declined estimated glomerular filtration rate (eGFR) over ADCmedulla, ΔADC and renal compartment volumes with an AUC of 0.904 (sensitivity of 83% and specificity of 91%) and was moderately correlated with the clinical biomarkers eGFR and proteinuria (P<0.05). The Cox survival analysis demonstrated that ADCcortex rather than ΔADC is a predictor of renal outcomes with a hazard ratio of 3.4 (95% CI: 1.1-10.2, P<0.05) independent of baseline eGFR and proteinuria. ADCcortex is a valuable imaging marker for the diagnosis and prediction of renal function decline in DKD.

A mechanical biosensor based on membrane-mediated magneto-stress-electric coupled sensitization for human serum albumin detection.

Recently, mechanical biosensors have attracted more attention on single molecule detection due to its high accuracy, low cost, and convenience. However, the sensitivity of the mechanical biosensors restricted their clinical application. Herein, a mechanical biosensor based on membrane-mediated magneto-stress-electric coupled sensitization (MSEC-MMB) was developed to enhance performance. Through introducing Fe3O4 nanoparticles (MNPs) to traditional stress-electric biosensors and applying a magnetic field, a magneto-stress-electric coupled biosensing system was constructed. The sensitivity of the MSEC-MMB was improved via enhancing the deformation of the mechanical membrane, which was demonstrated by detecting HSA. The optimal limit of detection (LOD) was 24 pg mL-1 under a magnetic field of 50 mT. The LOD was significantly 1 order of magnitude lower than that without the magnetic field. Besides, the MSEC-MMB showed a high specificity, selectivity, and stability. The clinical proteinuria samples were accurately detected, suggesting a good practicability of the MSEC-MMB. All these results proved the high sensitivity and practicality of the MSEC-MMB and provide a platform for early nephropathy diagnosis.

Re-understanding and focusing on normoalbuminuric diabetic kidney disease.

Diabetes mellitus (DM) has grown up to be an important issue of global public health because of its high incidence rate. About 25% of DM patients can develop diabetic foot/ulcers (DF/DFU). Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease (ESKD). DF/DFU and DKD are serious complications of DM. Therefore, early diagnosis and timely prevention and treatment of DF/DFU and DKD are essential for the progress of DM. The clinical diagnosis and staging of DKD are mostly based on the urinary albumin excretion rate (UAER) and EGFR. However, clinically, DKD patients show normoalbuminuric diabetic kidney disease (NADKD) instead of clinical proteinuria. The old NADKD concept is no longer suitable and should be updated accordingly with the redefinition of normal proteinuria by NKF/FDA. Based on the relevant guidelines of DM and CKD and combined with the current situation of clinical research, the review described NADKD from the aspects of epidemiology, pathological mechanism, clinical characteristics, biomarkers, disease diagnosis, and the relationship with DF/DFU to arouse the new understanding of NADKD in the medical profession and pay attention to it.

The genetic side of diabetic kidney disease: a review.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, with approximately 30-40% of patients with type 1 diabetes mellitus and 20% of patients with type 2 diabetes mellitus eventually developing DKD. If DKD is not controlled in the early clinical stage and proteinuria develops, the disease will progress to end-stage renal disease. The pathogenesis of DKD remains largely unknown and is multifactorial, likely due to interactions between genetic and environmental factors. Familial clustering also supports a critical role of hereditary factors in DKD. The development of gene detection technology has promoted the exploration of DKD susceptibility genes in different cohorts of patients with diabetes. Identifying susceptibility genes can provide insights into the pathogenesis of DKD, as well as a basis for its clinical diagnosis and therapy. Numerous candidate gene loci have been found to be associated with DKD, many of which play critical regulatory roles in the pathogenesis of this disease, including genes involved in glycol-metabolism, lipid metabolism, the renin-angiotensin-aldosterone system, inflammation and oxidative stress. In this review, we summarize the functions of several susceptibility genes involved in the development of DKD. Based on our findings, we recommend that studying susceptibility gene polymorphisms can lead to a better understanding of the pathogenesis of DKD and could help prevent this disease or improve its outcomes.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS)

BackgroundPrognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items.MethodsMachine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder–decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood.ResultsTime-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort.ConclusionsFour kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

MO251: Renal Glucocorticoid Receptor Expression and Clinical Course in Patients with IGA Nephropathy

Abstract BACKGROUND AND AIMS Glucocorticoids are used as primary treatment in IgA nephropathy (IgAN), and they manifest their effects by binding to intracellular glucocorticoid receptors. Studies have shown that GCR expression correlates with the degree of steroid response in various diseases. Therefore, we aimed to evaluate renal GCR expression, Oxford MEST score in clinical course of IgAN patients. METHOD This study included 110 patients with biopsy-proven IgAN. Patients were treated with ACEI/ARB, methylprednisolon (80% patients). In renal biopsies, Oxford-MEST score was calculated and GCR expression was determined immunohistochemically. KDIGO criteria (2020) were accepted for remission. Clinical course, eGFR, proteinuria and other biochemical tests test were recorded during 1-year follow-up period. RESULTS Demographic and laboratory data did not correlate with renal GCR staining rate. İn patients with M1 of the MEST score, GCR staining was more prominent than those with M0. GFR values were higher and proteinuria was lower in patients with T0 compared with patients with T1 and T2 (P &amp;lt; .05 for all) . Patients with E1 had significantly higher systolic blood pressure (BP), increased proteinuria and lower eGFR than patients with E0. Poor prognostic factors for achieving remission were higher systolic/diastolic BP, increased levels of white blood cell (WBC) count/neutrophil count, PTH, BUN, creatinine, uric acid, potassium, magnesium, MCV, Mentzer index, total cholesterol, LDL and higher sclerosis in biopsy at baseline during follow up period for 1 year. CONCLUSION Clinical presentation and outcome at 1 year in IgAN patients were well predicted by the Oxford-MEST score, but not by renal GCR expression. GCR staining intensity was only correlated with M1 score. Baseline higher BP, increased serum creatinine, uric acid and PTH were poor prognostic factors. Interestingly higher WBC and neutrophils counts, increased serum LDL and Mentzer index at baseline were also correlated with clinical course.

STUDY OF CORRELATION OF RETINOPATHY AND MICROALBUMINURIA IN PATIENT OF ESSENTIAL HYPERTENSION

Background: Hypertension is one of the leading causes of global burden of disease. Essential hypertension produces clinical proteinuria and microalbuminuria and is an early sign of kidney disease. Microalbuminuria has been shown to be a marker for end organ damage and results in retinopathy in the eye. Aims: The aim of the study was to determine the correlation between microalbuminuria and hypertensive retinopathy in patients of essential hypertension. Methods:This cross-sectional study was performed in 100 patients with essential hypertension of a tertiary care teaching hospital in eastern India, conducted between July 2020 to June 2021. Urinary albumin excretion was assessed by turbidimetry method and fundus was examined for grading of hypertensive retinopathy Result: Microalbuminuria was found to be present in 36 % patients of whom 65 % were males and 35% were females. Hypertensive retinopathy was observed in 66.7 % (24) patients, out of which 36 % patients had associated microalbuminuria. (p=0.001871) Conclusion: Investigation must be initiated for evidence of early renal disease in hypertensive patients to prevent MA and the resultant end organ damage. Furthermore, MA had a signicant correlation with retinopathy therefore fundus examination should be undertaken to predict the presence of ongoing vascular damage which can prevent atherosclerotic processes in the entire vascular system