24-hour Urinary Protein Excretion Research Articles

Association of HbA1c Variability with Vibrating Perception Threshold in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

To investigate the relationship between HbA1c variability and vibrating perception threshold (VPT) in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). A total of 367 middle-aged and elderly patients with T2DM were enrolled. All patients were categorized into the control and vibration sensation deficiency group (VSD) based on VPT. Clinical data were collected. The coefficient of variation of glycated hemoglobin A1c (HbA1c-CV) and the mean glycated hemoglobin A1c(HbA1c-Mean) are considered as indexes of HbA1c variability. Multivariate logistic regression analysis, the generalized linear model and ROC curve correlation analysis were used to analyze the correlation of various factors and VPT. The multivariate logistic regression analysis revealed that age, systolic blood pressure (SBP), and HbA1c-CV were identified as risk factors for vibration sensation deficiency in middle-aged and elderly patients with T2DM, while estimated glomerular filtration rate (eGFR), triiodothyronine (T3), and alanine aminotransferase (ALT) were considered as protective factors. In the unadjusted generalized linear model, a significant association was observed between HbA1c-CV and VPT values. After adjusting for age, diabetic duration, SBP, homeostatic model assessment for beta-cell function (HOMA-β), ALT, eGFR, T3, 24-hour urinary protein excretion levels, and HbA1c-Mean, HbA1c-CV remained significantly correlated with VPT values on both sides. (left side, B=2.560, 95% CI 1.298~3.823; P<0.001; right side, B=2.608, 95% CI 1.498~3.718, P<0.001). The area under the curve (AUC) for HbA1c-CV and VSD prevalence was 0.723, with a sensitivity of 79.85%, specificity of 56.22%. The risk of developing VSD increases proportionally with higher HbA1c-CV levels in middle-aged and elderly patients with T2DM. Reaching and maintaining blood glucose stability is essential to the mitigation of diabetes peripheral neuropathy occurrence.

Advancing Treatments for Rare Renal Diseases: New Hopes and Opportunities to Address a High Unmet Need

Introduction: The etiology of chronic kidney disease (CKD) is varied and complex. Diabetes and hypertension comprise 2/3 of cases and rare conditions, including inherited genetic diseases, comprise 1/3. We previously reported a 54% increase in clinical studies in CKD in the last 10 years. Hypothesizing a greater increase in rare renal disease studies, we undertook further analysis of metadata from Clinicaltrials.gov. Methods: CT.gov was searched for 49 conditions determined to be rare renal diseases posted between Jan-2003 and Dec-2022. Studies were divided into 2 time periods: P1 (2003–2012) and P2 (2013–2022) and analyzed by study type, phase, indication, primary endpoint, population, and funding. Results: Studies increased significantly in P2 versus P1 (123%, p < 0.001) with the greatest rise in observational studies (283%, p < 0.001). Interventional studies increased 93% (p < 0.01), with the greatest rise in early phases (205%, p < 0.001). The most frequent indications were LN, ADPKD, and IgA nephropathy; all increased 77–166% in P2 (p < 0.05 – p < 0.001). Proteinuria was the most frequent primary endpoint, which increased 63% (p = 0.054). Studies with pediatric populations increased 78% (p < 0.01). Most studies were nonindustry funded; however, industry-funded studies increased by 225% (p < 0.001). Conclusion: Clinical research in rare renal diseases has increased significantly in the last 10 years, particularly in glomerular diseases (GDs) and ADPKD. Proteinuria correlates with outcomes in GD, which explains the high percentage of studies with this primary endpoint. Rare renal diseases disproportionately affect children and the rise in studies with pediatric populations is encouraging. The rise in observational studies may signal an increased focus on understanding the natural course and pathophysiology of disease, which may lead to new potential therapeutic targets and future interventional studies. The increase in industry-funded studies suggests basic science is translating into industry-sponsored research.

Twenty-four-hour urinary protein excretion in uncomplicated singleton pregnancy

Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6+0 to 13+6, 14+0 to 27+6, and 28+0 to 41+6 weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (≥35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6-100.0) vs 70.5 (50.5-100.0) mg, 85.8 (62.0-117.0) vs 96.0 (68.0-127.8) mg, and 106.6 (76.0-146.2) vs 114.7 (81.5-153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management.

Homeostatic Modulation of CD4+ T Cell Subsets Using the Chinese Medicine Jianpi Qushi Heluo Formula During the Alleviation of Primary Membranous Nephropathy

ABSTRACT Background: Compelling evidence suggests that the immune system plays a key role in the development and progression of primary membranous nephropathy (pMN). The Jianpi Qushi Heluo Formula (JQHF) is an empirical and effective traditional Chinese medicine prescription used for the clinical treatment of pMN in China. However, it remains unclear whether JQHF treatment affects the peripheral immune system of patients with pMN. Methods: Twenty-five patients with pMN and 10 healthy controls (HC) were enrolled. Patients with pMN were treated with JQHF for 6 months. Circulating CD4+ T cell subsets and associated chemokines were analyzed using flow cytometry among both HC and pMN before and after 6 months of JQHF treatment. Results: Patients with pMN treated with JQHF achieved 60% clinical remission and a significant reduction in 24-hour urinary protein excretion (24hUTP). Compared to HC, Th1 cells increased, Treg cells decreased, and Th1/Th2, Th1/Treg, and Th17/Treg cells increased in the pMN (P = 0.011, P = 0.035, P = 0.001, P = 0.026, P = 0.038, respectively). JQHF treatment significantly improved cellular immune imbalance in patients with pMN. Patients with pMN showed increased levels of peripheral blood C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, and C-C motif ligand 20 (CCL20), but no significant difference was observed compared with HC. JQHF treatment significantly reduced CXCL10 levels (P = 0.0071). Moreover, 24hUTP was strongly and positively correlated with Th1 cell and CXCL10 levels (P = 0.0438 and P = 0.0211, respectively). Total serum protein levels were strongly and positively correlated with Tregs (P = 0.0816). Th1 cells also strongly and positively correlated with CXCL10 levels (P = 0.0012). Conclusion: Our findings suggest an imbalance in the immune differentiation of peripheral blood CD4+ T cells in patients with pMN. JQHF treatment had a pronounced effect on pMN, which may be mediated by the improvement of homeostatic modulation of CD4+ T cell subsets.

CORRELATION OF 24-HOUR URINARY PROTEIN TO SPOT URINARY PROTEIN TO CREATININE RATIO AT DIFFERENT TIMES OF THE DAY IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Spot urine protein to creatinine ratio has become a conventional measure of daily protein excretion in patients with chronic kidney disease (CKD). It is easily obtained and is reproducible. However, the values may vary with the time of the day, and collecting the first-morning void is typical. Twenty-four hours of urinary protein has been the traditional gold standard test for estimating protein excretion. This test is still carried out in centers where spot measurements are unavailable. We conducted our study to determine the correlation between 24-hour urinary protein and spot urinary protein to creatinine ratio at different times of the day (early morning, afternoon, and night). Sixty-seven patients of CKD fulfilling the inclusion criteria were asked to provide 24-hour urine samples according to standard recommendations. According to protocol, small aliquots of urine samples (5 ml each) were taken from the 24-hour sample to be processed for spot urinary protein and creatinine. Data was analyzed on SPSS version 22 and is presented as numbers, means + SD (age, spot urinary protein to creatinine ratio for morning, afternoon, and night), and frequencies (gender, type of kidney disease). Pearson's 'r' was tested for a significant correlation between 24 hours of urine protein and all different samples of spot collections. In contrast, sensitivity and specificity for spot urine protein-to-creatinine ratio predicting 24-hour protein excretion of &lt;1, 1 – 3.5, and &gt;3.5 g/day were determined using receiver operating characteristic curves (ROC Curves). In our cohort of patients across all stages of chronic kidney disease, we observed that there was a strong correlation between all three protein-to-creatinine ratio samples with 24 hours of urinary protein excretion; however, nighttime protein creatinine ratio showed the strongest correlation with 24 hours of urinary protein excretion (Pearson's r: 0.797). Nighttime spot urine protein to creatinine ratio sample was also found to have the highest sensitivity across all 24-hour urinary protein excretion levels.A nighttime spot urinary protein to creatinine ratio sample may reliably predict 24 hours of urinary protein excretion.

Ofatumumab in Rituximab-Resistant and Rituximab-Intolerant Patients With Primary Membranous Nephropathy: A Case Series

Rituximab is the first-choice therapy for patients with primary membranous nephropathy (MN) and nephrotic syndrome. However, approximately 30% of patients are treatment-resistant or become treatment-intolerant with hypersensitivity reactions upon repeated drug exposures. We aimed to assess whether ofatumumab, a fully human second-generation anti-CD20 antibody, could be a valuable alternative to rituximab in this population. Case series. 7 rituximab-intolerant and 10 rituximab-resistant patients with MN who consented to receive ofatumumab (50-300mg, single intravenous infusion) and were followed at the nephrology unit of Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII (Bergamo, Italy) between September 2015 and January2019. Over a median (IQR) follow-up of 5.0 (3.0-9.8) months, all 7 rituximab-intolerant and 3 of the 10 rituximab-resistant patients exhibited complete (proteinuria<0.3g/d) or partial (proteinuria<3.5g/d with≥50% reduction vs baseline) remission of nephrotic syndrome. Circulating B cells were similarly depleted in all patients by 1 week, and serum anti-phospholipase A2 receptor antibody concentrations decreased to<2.7 relative units/mL in 3 of 4 rituximab-intolerant and 4 of 8 rituximab-resistant patients with phospholipase A2 receptor-related disease. Ofatumumab significantly reduced 24-hour urinary protein and immunoglobulin G excretion and increased serum albumin and immunoglobulin G levels. These effects were greater in rituximab-intolerant than in rituximab-resistant patients. Measured glomerular filtration rate significantly increased by an average of 13.4% at 24 months compared with baseline (P=0.036) among all patients in the series. There were 14 nonserious infusion-related adverse events in 9 patients that recovered with temporary infusion interruption. Retrospective design, limited number of patients. Ofatumumab may represent an effective and safe treatment for rituximab-intolerant cases of MN. Larger prospective studies will be needed to validate these preliminary findings and explore the effectiveness of other second-generation anti-CD20 antibodies in this clinical setting. Primary membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome (NS) in adults. In this case series, we explored the efficacy of ofatumumab, a fully human second-generation anti-CD20 antibody, in 17 patients with MN and NS who were intolerant or unresponsive to rituximab. All 7 rituximab-intolerant patients exhibited complete or partial clinical remission, compared with only 3 of the 10 rituximab-resistant patients. Autoantibody levels decreased in all patients with phospholipase A2 receptor-related disease. Ofatumumab achieved a significant reduction in urinary protein and immunoglobulin G excretion while increasing serum albumin and immunoglobulin G levels. Ofatumumab may be a promising option for patients with MN who are rituximab-intolerant. Further investigations are warranted to validate these preliminary findings.

Comparison of Spot Urinary Protein Creatinine Ratio and 24 hour Urinary Protein Excretion in Children presenting with Nephrotic Syndrome in Tertiary Care Hospital of Eastern Nepal

Introduction: Nephrotic syndrome is an important chronic disorder in children and it’s one of the important diagnostic criteria is presence of heavy proteinuria (&gt; 40 mg/m2/hour). As 24-hour urinary protein estimation is cumbersome, inconvenient, time consuming and expensive, a more convenient and accurate method of urinary protein estimation is needed. 24-hour urinary protein estimation and urine protein/creatinine in a child with nephrotic syndrome correlates well but there are very few studies done in Nepal to prove this correlation. Hence, this study is undertaken with objective of evaluating usefulness of urine protein/creatinine (UP/UC) in random sample of urine as a rapid and reliable test for quantification of proteinuria and to know their correlation with 24hour urinary protein excretion. Objectives: Primary Objective: To evaluate accuracy of urine protein creatinine ratio (UP/UC) in early morning sample in comparison with 24 hours urinary protein excretion in children of nephrotic syndrome having normal Glomerular Filtration Rate. Secondary Objective: To evaluate usefulness of urine protein / creatinine ratio (UP/UC) in random sample of urine as rapid and reliable test for quantification of proteinuria. To evaluate biochemical and other laboratory abnormalities in children with nephrotic syndrome. To study varied clinical presentation of Pediatric nephrotic syndrome Methodology: This is a descriptive cross-sectional study conducted in pediatric unit, Nobel Medical College Teaching Hospital, Biratnagar for 12 months. In this study, 50 patients of both sexes, ranging from one to fifteen years of age were studied. The modes of presentation, laboratory investigation reports which included urine routine microscopy, 24-hour urine protein estimation, urine protein / creatinine in random sample of urine were documented and data was analyzed by linear regression. Results: Linear regression revealed that as timed 24-hour urine protein in gm/24 hour increased, Random urine/protein creatinine ratio mg/mg also increased linearly with correlation coefficient of r = 0.56 which was highly significant (p &lt; 0.001). Conclusion: This study concludes that UP/UC ratio in a spot urine reflects the amount of protein in 24-hour urine collection. UP/UC ratio &gt; 2 in patients with normal renal function represents nephrotic range proteinuria.

#4124 SEX AND CARDIOVASCULAR DISEASE IN STAGE G2-5 CKD PATIENTS

Abstract Background and Aims Male sex is considered a major risk factor for cardiovascular (CV) disease in the general population, but the role of this factor in the high risk for CV disease in the pre-dialysis CKD population is still debated. Methods We tested the relationship between sex and fatal and non-fatal major CV events (myocardial infarction, heart failure, arrhythmia, angina, stroke, transient ischemic attack, peripheral vascular disease, major arterial or venous thrombotic episodes and sudden death) in a cohort including 759 stage 2-5 CKD consecutively recruited from 22 Nephrology units in southern Italy between October 2005 and September 2008. After the initial assessment, patients were followed up for a median time of 36 months (range 0.3–48 months). Results Four hundred fifty-five patients were males (60%). The proportion of smokers was about 4 times higher in males (71.4%) than in females (17.4%). Males and females differed in the prevalence of diabetes (38.5% versus 29.6%) and the frequency of background CV comorbidities (35.6% versus 19.7%, P&amp;lt;0.001). Waist circumference (100.9±12.4 versus 96±14.1 cm), eGFR (37.5±13.4 versus 33±12.7 ml/min/1.73 m2), 24-hour urinary protein excretion (median: 0.7 g/24h, IQR: 0.2-1.6 g/24h versus 0.5, IQR: 0.2-1.2 g/24 h), and haemoglobin (13.4±1.9 versus 12.0±1.4 g/dL) were higher in males than in females. Serum phosphate (3.6±0.75 versus 3.9±0.75 mg/dL), hs-CRP (median; 2.2 mg/dl, IQR: 1-4.7mg/dl versus 2.8 mg/dl, IQR: 1.2-6.4 mg/dl) and total cholesterol (178.3±42.1 versus 198.8±45.6 mg/dl) were lower in males than in females. During follow-up, 42 patients died, and 118 had fatal and non-fatal CV events. On univariate Cox regression analyses, male gender failed to be associated with all-cause mortality but was strongly related to the incidence rate of fatal and non-fatal major CV events [HR 1.75, 95% CI: 1.18-2.60, P=0.006]. Data adjustment for a series of major potential confounders did not materially affect the strength of this relationship [HR:1.78, 95% CI: 1.03-3.09]. Further analysis testing the effect of age on major CV outcomes by gender showed an effect modification by this risk factor on the same outcome (P=0.037) because the hazard ratio of male versus female CV events increased progressively with ageing (Figure 1). Conclusion The excess risk for CV mortality by the male gender in the general population holds in stage G2-5 CKD patients. Age is a modifier for the excess risk for CV events in CKD patients because the risk excess of the male gender increases linearly across a wide age spectrum in CKD patients.

#5215 OFATUMUMAB AS A RESCUE THERAPY FOR PATIENTS WITH MEMBRANOUS NEPHROPATHY

Abstract Background and Aims Rituximab is the first-line treatment for patients with primary membranous nephropathy (MN) and nephrotic syndrome (NS) at high risk of progression to end-stage kidney disease. However, this drug is effective only in approximately two thirds of treated patients, and repeated rituximab infusions may be complicated by hypersensitivity reactions, which contraindicate retreatment. Ofatumumab, a fully human anti-CD20 antibody, could overcome these limitations. Method We retrospectively evaluated the response to a single 50–300 mg dose of intravenous ofatumumab in 17 MN patients referred to our institution who either experienced hypersensitivity reactions (rituximab-intolerant, n = 5) or failed to achieve NS remission after rituximab infusion (rituximab-resistant, n = 12). Results Over a median [IQR] follow-up of 5.0 [3.0-9.8] months, ten (58.8%) patients—five rituximab-resistant (41.7%) and all five rituximab-intolerant—achieved complete or partial NS remission, defined as proteinuria &amp;lt;0.3 g/day or proteinuria &amp;lt;3.5 g/day with ≥50% reduction from baseline, respectively. Ofatumumab infusion induced a progressive reduction in 24-hour urinary protein and IgG excretion, and a sharp increase in serum albumin and IgG levels. Peripheral B cells were depleted in all patients and started reconstituting by 3 months from baseline. Seven of the 12 subjects with PLA2R-related disease (i.e. with baseline anti-PLA2R antibody levels &amp;gt;2.7 RU/mL by ELISA) achieved antibody depletion during the follow-up (half of rituximab-resistant and all rituximab-intolerant). There were 14 non-serious infusion-related adverse events in nine patients, all of which completely resolved with temporary interruption of ofatumumab infusion. Conclusion Ofatumumab may be an effective and safe treatment option for all rituximab-intolerant and a substantial proportion of rituximab-resistant MN patients.

Membranous nephropathy caused by dimercaptosuccinic acid in a patient with Wilson’s disease: a case report and literature review

BackgroundDimercaptosuccinic acid (DMSA) therapy is a kind of chelation therapy for patients with Wilson ‘s disease (WD). While there have been reports of side effects associated with DMSA, the development of membranous nephropathy as a result of this therapy is uncommon.Case presentationWe present a case of a 19-year-old male patient with Wilson’s disease who experienced proteinuria while receiving long-term DMSA treatment. Further evaluation revealed abnormally low levels of serum ceruloplasmin and serum albumin, as well as a 24-hour urinary protein excretion of 4599.98 mg/24 h. A renal biopsy confirmed the presence of membranous nephropathy. After ruling out other potential causes, we determined that the patient’s membranous nephropathy was likely caused by DMSA. Following treatment with glucocorticoids, there was a significant reduction in proteinuria.ConclusionThis case highlights the possibility of DMSA-induced membranous nephropathy and the importance of considering this diagnosis in patients receiving DMSA treatment. Given the widespread use of DMSA in the treatment of Wilson’s disease, further research is needed to fully understand the potential role of this drug in the development of membranous nephropathy.

The Correlation of Urine Protein/osmolality and Protein/creatinine Ratio as Predictor of 24-hour Urinary Protein Excretion.

The drawback of 24-hour urine collection is that it is troublesome, takes a lot of time, and is inaccurate because of collection errors and improper timing. The research in the Indian adult population about the correlation of spot urine protein/osmolality ratio (UPOR) and spot urine protein/creatinine ratio (UPCR) as a predictor of 24-hour urinary protein excretion is lacking. To study the correlation of spot UPOR and spot UPCR as the prognosticator of 24-hour urinary protein excretion. The present cross-sectional observational study was undertaken on 50 patients &gt;18 years of age and of either sex who presented with proteinuria (dipstick test or urine routine) and were advised 24-hour urine protein examination. A 24-hour urine was collected for protein analysis starting from any time of day. Random urine samples were collected and processed for protein, creatinine, and osmolality. The spot UPOR and UPCR were calculated. The sensitivity and specificity were determined. Pearson's correlation was used to find the correlation. There was a statistically significant positive correlation of UPOR and UPCR (r = 0.418 and r = 0.512, respectively) with 24-hour urinary protein excretion. The sensitivity and specificity of UPOR to predict 24-hour urinary protein at cutoff point 1.32 was 82.3% and 81%, respectively. The sensitivity and specificity of UPCR to predict 24-hour urinary protein at cutoff point 1.09 was 87 and 86%, respectively. For the medical determination of proteins in urine, spot UPOR and UPCR are suitable, cheap, and dependable methods that can substitute the measurement of 24-hour urine protein.

Correlation between 24-hour Urinary Total Protein Excretion and Single Urinary Protein Creatinine ratio in the Diagnosis of Childhood Nephrotic Syndrome : Study in a Tertiary Level Hospital

Introduction:Protein excretion varies in the course of the day, for this reason 24-hours urinary total protein excretion has been considered as the classic reference method for protein determination in nephotic syndrome. As the collection of urine for 24 hours is tedious and errors may occur during the process, so the protein:creatinine ratio was developed as a diagnostic alterative for Nephrotic syndrome.The main aim of this study is to determine the correlation between 24-hour urinary total protein excretion and single urinary protein creatinine ratio in childhood Nephrotic syndrome. Methods: This cross-sectional study was conducted in the department of Paediatrics,Shaheed Suhrawardy Medical College &amp; Hospital from June 2018 to May 2019. After taking valid consent total 60 cases of Nephrotic syndrome were selected purposively according to inclusion and exclusion criteria. Here we tried to determine the correlation between 24-hour urinary total protein excretion and single urinary protein creatinine ratio in the diagnosis of childhood Nephrotic syndrome by measuring the spot urinary protein creatinine ratio and the 24 hours urinary total protein excretion of the patients. Results : Among total 60(N) children of Nephrotic syndrome 42 (70%) patients were male and 18 (30%) patients were female with M:F = 2.16:1.The mean age was 4.57 ± 2.01SD years. Most of the patients were presented with some associated diseases like urinary tract infection (30%), upper respiratory tract infection (28.3%), viral illness(8.3%), atopic dermatitis(3.3%) and nonspecific illnesses(30%). The main physical findings were only puffy face(100%), with ascites (86.6%) and swelling of genitalia (38.3%).The mean 24 hours urinary total protein excretion was 3114.45 ± 1627.89 mg/24 hours and spot urinary protein creatinine ratio was 5.57 ± 3.13 SD. There was a very significant correlation between 24 hour total urinary protein excretion and spot urinary protein creatinine ratio. The sensitivity of the study was 80.49 – 100% and specificity of 91.78 - 100% at £2000 mg /sqm body surface area/ day protein excretion. The p value was .002 with correlation coefficient was 0.39. Conclusion: The protein creatinine ratio of a random urine sample might be used as an alternative method for the diagnosis of Nephrotic syndrome in children in view of the obvious advantages in terms of cost, time and patient convenience. J Shaheed Suhrawardy Med Coll 2021; 13(2): 137-142

Effects of receiving renal biopsy on the prognosis of chronic kidney disease patients with impaired renal function

BackgroundImpaired renal function was not a recognized indication for renal biopsy. The effects of receiving renal biopsy on the renal functional prognosis for chronic kidney disease (CKD) patients with impaired renal function need to be explored.MethodsThis study retrospectively enrolled 300 renal function impaired CKD patients in Renji Hospital from January 2015 to December 2017, 150 of them received percutaneous renal biopsy while the others did not. The endpoint was ≥ 50% estimated glomerular filtration rate (eGFR) decline from baseline or development of end-stage renal disease (ESRD). Kaplan-Meier analysis with log-rank test was performed to compare the renal survival probability between patients receiving renal biopsy or not. Univariate and multivariate analysis with Cox regression were conducted with predictors of poor renal outcomes in the study cohort.ResultsThe median follow-up period was 37.6 months. During the follow-up period, the eGFR of the biopsy group increased from 52.2 ± 14.4 to 67.4 ± 37.8 ml/min/1.73 m², but decreased from 55.3 ± 17.1 to 29.8 ± 19.1 ml/min/1.73 m² in the non-biopsy group. Patients who received renal biopsy had significantly higher renal survival probability (P < 0.001). Cox regression analysis revealed that 24-hour urine protein excretion (24 h UPE) more than 1 g/d was an independent predictor for poor renal outcomes in the non-biopsy group but not in the renal biopsy group (HR = 1.719, P = 0.040).ConclusionCKD patients with impaired renal function are recommended to receive renal biopsy to make pathological diagnoses, especially for those with the 24-hour urine protein excretion more than 1 g/d.

Proteinuria Modifies the Relationship Between Urinary Sodium Excretion and Adverse Kidney Outcomes: Findings From KNOW-CKD

High sodium intake is associated with increased proteinuria. Herein, we investigated whether proteinuria could modify the association between urinary sodium excretion and adverse kidney outcomes in patients with chronic kidney disease (CKD). In this prospective observational cohort study, we included 967 participants with CKD stages G1 to G5 between 2011 and 2016, who measured 24-hour urinary sodium and protein excretion at baseline. The main predictors were urinary sodium and protein excretion levels. The primary outcome was CKD progression, which was defined as a≥50% decline in the estimated glomerular filtration rate (eGFR) or the onset of kidney replacement therapy. During a median follow-up period of 4.1 years, the primary outcome events occurred in 287 participants (29.7%). There was a significant interaction between proteinuria and sodium excretion for the primary outcome (P= 0.006). In patients with proteinuria of<0.5 g/d, sodium excretion was not associated with the primary outcome. However, in patients with proteinuria of≥0.5 g/d, a 1.0 g/d increase in sodium excretion was associated with a 29% higher risk of adverse kidney outcomes. Moreover, in patients with proteinuria of≥0.5 g/d, the hazard ratios (HRs) (95% confidence intervals[CIs]) for sodium excretion of<3.4 and≥3.4 g/d were 2.32 (1.50-3.58) and 5.71 (3.58-9.11), respectively, compared with HRs for patients with proteinuria of<0.5 g/d and sodium excretion of<3.4 g/d. In sensitivity analysis with 2 averaged values of sodium and protein excretion at baseline and third year, the results were similar. Higher urinary sodium excretion was more strongly associated with an increased risk of adverse kidney outcomes in patients with higher proteinuria levels.

Protein restriction for diabetic kidney disease.

Diabetic kidney disease (DKD) continues to be the leading cause of kidney failure across the world. For decades dietary protein restriction has been proposed for patients with DKD with the aim to retard the progression of chronic kidney disease (CKD) towards kidney failure. However, the relative benefits and harms of dietary protein restriction for slowing the progression of DKD have not been addressed. To determine the efficacy and safety of low protein diets (LPD) (0.6 to 0.8 g/kg/day) in preventing the progression of CKD towards kidney failure and in reducing the incidence of kidney failure and death (any cause) in adult patients with DKD. Moreover, the effect of LPD on adverse events (e.g. malnutrition, hyperglycaemic events, or health-related quality of life (HRQoL)) and compliance were also evaluated. We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included randomised controlled trials (RCTs) or quasi-RCTs in which adults with DKD not on dialysis were randomised to receive either a LPD (0.6 to 0.8 g/kg/day) or a usual or unrestricted protein diet (UPD) (≥ 1.0 g/kg/day) for at least 12 months. Two authors independently selected studies and extracted data. Summary estimates of effect were obtained using a random-effects model. Results were summarised as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised MD (SMD) with 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We identified eight studies involving 486 participants with DKD. The prescribed protein intake in the intervention groups ranged from 0.6 to 0.8 g/kg/day. The prescribed protein intake in the control groups was ≥ 1.0 g/kg/day, or a calculated protein intake ≥ 1.0 g/kg/day if data on prescribed protein intake were not provided. The mean duration of the interventions was two years (ranging from one to five years). Risks of bias in most of the included studies were high or unclear, most notably for allocation concealment, performance and detection bias. All studies were considered to be at high risk for performance bias due to the nature of the interventions. Most studies were not designed to examine death or kidney failure. In low certainty evidence, a LPD may have little or no effect on death (5 studies, 358 participants: RR 0.38, 95% CI 0.10 to 1.44; I² = 0%), and the number of participants who reached kidney failure (4 studies, 287 participants: RR 1.16, 95% CI 0.38 to 3.59; I² = 0%). Compared to a usual or unrestricted protein intake, it remains uncertain whether a LPD slows the decline of glomerular filtration rate over time (7 studies, 367 participants: MD -0.73 mL/min/1.73 m²/year, 95% CI -2.3 to 0.83; I² = 53%; very low certainty evidence). It is also uncertain whether the restriction of dietary protein intake impacts on the annual decline in creatinine clearance (3 studies, 203 participants: MD -2.39 mL/min/year, 95% CI -5.87 to 1.08; I² = 53%). There was only one study reporting 24-hour urinary protein excretion. In very low certainty evidence, a LPD had uncertain effects on the annual change in proteinuria (1 study, 80 participants: MD 0.90 g/24 hours, 95% CI 0.49 to 1.31). There was no evidence of malnutrition in seven studies, while one study noted this condition in the LPD group. Participant compliance with a LPD was unsatisfactory in nearly half of the studies. One study reported LPD had no effect on HRQoL. No studies reported hyperglycaemic events. Dietary protein restriction has uncertain effects on changes in kidney function over time. However, it may make little difference to the risk of death and kidney failure. Questions remain about protein intake levels and compliance with protein-restricted diets. There are limited data on HRQoL and adverse effects such as nutritional measures and hyperglycaemic events. Large-scale pragmatic RCTs with sufficient follow-up are required for different stages of CKD.

Measurement of urinary protein in children

Proteinuria is an early hallmark of kidney disease and a major risk factor for systemic cardiovascular diseases. There are several methods to measure proteinuria, such as the urine dipstick test, 24-hour urinary protein excretion method, and spot urine for the protein-to-creatinine ratio. The urine dipstick test is simple but inaccurate. The 24-hour urinary protein excretion method is the gold standard; however, it is cumbersome, especially in children. Spot urine for the protein-to-creatinine ratio is simple and accurate, but has limitations. Specific urinary protein such as albumin can be measured instead of the total protein content. Tests should be avoided in situations that cause transient proteinuria or false-positive results. It should be performed correctly, and its limitations should be recognized and interpreted accurately.

Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch-Schönlein Purpura Nephritis.

Henoch-Schönlein purpura nephritis (HSPN) is considered a major cause of chronic renal failure and is the most common secondary glomerular disease in children. Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects against HSPN in clinical practice. However, the potential molecular targets and mechanisms underlying HSPN treatment remain unclear. By constructing a protein-protein interaction (PPI) network, core targets related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways related to HSPN based on the core targets. To screen the main active ingredients of HQH against HSPN, an ingredient-target-pathway network was constructed using the top 10 main pathways associated with HSPN. Then, molecular docking was performed to explore the interactions and binding patterns between molecules and proteins. Clinical data showed that HQH combined with conventional medicine significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15 potential core targets were identified. The top 10 main pathways showed higher enrichment ratios, including the cytokine-cytokine receptor interaction and signaling pathways related to NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and molecular docking, we revealed that five active ingredients of HQH had good affinities with three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. The study preliminarily explored the active ingredients, targets, and pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be attributed to the modulation of inflammatory response, immune response, and oxidative stress. Combined with clinical data, our results indicate that HQH is highly effective in treating HSPN.

The Roles of Heat Shock Protein-60 and 70 and Inflammation in Obesity-Related Kidney Disease.

IntroductionThe exact mechanisms of obesity-related kidney disease (ORKD) are not fully known. Heat shock proteins (HSPs) may play a role in ORKD mechanisms because of their role in cell apoptosis, cytoprotection, and inflammatory processes. We aimed to determine the role of circulating serum HSP-60 and HSP-70 levels as a biomarker for ORKD.Materials and methodsThis study included 40 ORKD patients, 40 obese age-matched and sex-matched controls with similar body mass index (BMI), and 40 healthy controls. Their serum biochemical and hemogram parameters as well as HSP-60 and HSP-70 levels were evaluated and compared. Their neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein levels were assessed to define inflammation. ResultsThe patients had significantly higher HSP-60 levels than the obese and healthy controls (537.58 ± 170.35, 430.80 ± 110.61, and 371.85 ± 76.34, respectively; p<0.00). The results revealed that the 24-hour urinary protein levels had a positive correlation (r= 0.544), whereas the glomerular filtration rate had a negative correlation (r = 0.38) with the serum HSP-60 level. According to the regression analysis performed on the HSP-60 and 24-hour urinary protein excretion levels, an increase in the HSP-60 level significantly increased the 24-hour urinary protein excretion rate (r=0.15; p<0.005). The HSP-60 levels were correlated with inflammatory markersConclusionThe serum HSP-60 levels increased in patients with ORKD. This increase was correlated with 24-hour urinary protein excretion. Increased circulating levels of HSP-60 may play a role in the initiation and/or progression of renal damage and inflammation. HSP-60 is a potential biomarker for ORKD. However, additional information and studies are required to further elucidate this finding.

Assessment of renal microcirculation in biopsy-proven tubulointerstitial nephritis in patients with and without glomerular disease: the role of resistive index.

Renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status and it is associated with changes in renal function. Aim of the study was to assess RRI in biopsy-proven tubulointerstitial nephritis (TIN) in patients with and without glomerular disease. 132 consecutive patients underwent to native renal biopsy with diagnosis of isolated TIN or in association with glomerulonephritis. Estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion and renal ecocolorDoppler ultrasonography with RRI assessment were performed at time of enrollment. Patients with isolated-TIN had significantly higher RRI than both patients with non-immunoglobulin A glomerulonephritis (non-IgA-TIN) [0.73 (0.68-0.77) vs 0.64 (0.60-0.67), p<0.001] and patients with IgA nephropathy (IgAN) [0.73 (0.68-0.77) vs 0.66 (0.60-0.71), p<0.01]. Patients with isolated-TIN had mainly RRI≥0.70 (n=15, 65.2%) with the respect to patients with non-IgA-TIN (n=7, 12.3%) and patients with IgAN (n=17, 32.7%). A negative linear correlation was found between RRI and hemoglobin (r=0.233, p<0.01) and between RRI and eGFR (r=0.537, p<0.001). Tubulointerstitial damage is the most accurate histological lesion that correlates with eGFR and renal impairment. RRI can be a useful parameter to detect tubulointerstitial lesions.

POS-045 Evaluating BCX9930, an Oral Factor D Inhibitor for Treatment of Complement-Mediated Kidney Disease: A Proof-of-Concept Study (RENEW)

POS-045 Evaluating BCX9930, an Oral Factor D Inhibitor for Treatment of Complement-Mediated Kidney Disease: A Proof-of-Concept Study (RENEW)