24-h Urinary Protein Excretion Research Articles

Baseline renal functions predict the effect of canakinumab on regression of proteinuria in patients with familial Mediterranean fever

Introduction and objectivesCanakinumab, an IL-1 blocking drug, decreases the frequency and severity of the attacks and decreases the proteinuria level in colchicine resistant/intolerant familial Mediterranean fever (FMF) patients. However, it is not known whether patients with impaired or preserved renal functions respond differently to IL-1 blocking therapies in terms of proteinuria reduction and progression of kidney dysfunction which was the aim of this study. Materials and methodsAdult FMF subjects with biopsy proven amyloidosis who had 24-h urine protein excretion>150mg/day before initiation of canakinumab were divided into two groups as patients with preserved renal function (GFR≥60mL/min) and patients with impaired renal function (GFR<60mL/min). The response in proteinuria and renal functions are compared between two groups in this cross-sectional study. ResultsA total of 18 patients (11 with preserved and 7 with impaired renal function) were included in this study. Although proteinuria levels of both groups were similar at the baseline and at six months after initiation of canakinumab, proteinuria at 12 months was significantly lower for patients with preserved renal function compared to patients with impaired renal function (2462±1760mg/day vs. 7065±3035mg/day respectively, p=0.02). All of the patients with preserved renal function had more than 50% decrease in proteinuria at 12 months compared to baseline values, while none of the patients with impaired renal function had more than 50% decrease in proteinuria. ConclusionsCanakinumab, an IL-1 blocking agent, is not effective in decreasing proteinuria in FMF patients with already impaired renal functions and should be started early in the course of disease to prevent renal impairment.

Leflunomide plus low-dose prednisone in patients with progressive IgA nephropathy: a multicenter, prospective, randomized, open-labeled, and controlled trial

Background Immunoglobulin A nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, and the optimal approach to its treatment remains a significant challenge. Methods We did a prospective, randomized, open-labeled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment, and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF + prednisone group) or conventionally accepted-dose prednisone [prednisone(alone) group] Our primary outcome was 24-h urine protein excretion (UPE) and secondary outcomes were serum albumin (sALB), serum creatinine (Scr), and eGFR. Safety was evaluated in all patients who received the trial medications. Results One hundred and eight patients [59 in LEF + prednisone group, 49 in prednisone (alone) group]were enrolled and finished their treatment and follow-up periods. There is no significant difference in the baseline level between the two groups. Compared with baseline, both groups showed a significant decrease in 24-h UPE (p < 0.01) and increase in sALB (p < 0.01), with stable Scr and eGFR throughout the 12-month treatment period. What’s more, these effects were sustained through the 12-month follow-up period. However, there was no difference in 24-h UPE, sALB, Scr, and eGFR between the two groups (p > 0.05). At 12 months, a difference in overall response rate, relapsing rate, and incidence of adverse events between the two groups was not significant. Conclusions The efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in the treatment of progressive IgAN are comparable.

Serum uric acid as a predictor for nephritis in Egyptian patients with systemic lupus erythematosus.

Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is considered a risk factor for renal involvement in systemic lupus erythematosus (SLE). This study aimed to examine the association between serum uric acid (SUA) level and LN development and progression in SLE patients with normal renal function. A total of 60 SLE patients with normal renal function from Ain Shams University Hospital were selected and assigned to group 1 (30 patients with LN) and group 2 (30 patients without LN). All patients were subjected to history taking, clinical examination, disease activity assessment based on SLE disease activity index (SLEDAI) and renal SLEDAI (SLEDAI-R) scores, and laboratory investigations, including as SUA, complete blood count, blood urea nitrogen (BUN), serum creatinine, creatinine clearance, urine analysis, protein/creatinine ratio, 24-h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). Disease duration, SLEDAI score, and SUA level were higher in group 1 than in group 2 (p < 0.001). SUA level was positively correlated with SLEDAI and SLEDAI-R scores, proteinuria, urinary casts, renal biopsy class, disease activity and chronicity indices, BUN level, and serum creatinine level but was negatively correlated with creatinine clearance (p < 0.05). SUA was a predictor of LN development in SLE patients (sensitivity, 83.3%; specificity, 70%). SUA is associated with the development of lupus nephritis in patients with normal kidney function also SUA in-dependently correlated with disease activity and chronicity in LN.

Uric acid as a risk factor for progression to chronic kidney disease in patients with lupus nephritis: results from the KORNET registry

Little is known regarding the effect of hyperuricaemia on the progression of kidney function in patients with lupus nephritis (LN). Thus, we investigated the effect of uric acid (UA) on the long-term outcome of patients with biopsy-proven LN. Data were obtained from KORNET, a prospective longitudinal systemic lupus erythematosus registry in the Republic of Korea. All 137 patients with LN included in this study had undergone a kidney biopsy and were subsequently treated with immunosuppressants. The patients were divided into two groups: UA ≤7 mg/dL and >7 mg/dL; their sociodemographic, clinical, treatment-related data, and outcomes were compared. Cox-proportional regression analyses were performed to identify independent predictors of renal outcome in patients with LN. Among the 137 patients, 37 (27.0%) had UA >7 mg/dL. This higher UA group included fewer women, but more patients with hypertension, proliferative type LN, and a chronicity index >12. The 24-h urinary protein excretion and the creatinine level were higher in this group; haemoglobin, platelet, and albumin levels were lower. During 85.0 months of follow-up, complete remission at 1 year was less frequent in the higher UA group, whereas chronic kidney disease (CKD) and end-stage renal disease were more prevalent. In the Cox proportional hazards regression analysis, UA >7 mg/dL was a signi cant predictor of progression to CKD in patients with LN (hazard ratio=2.437; p=0.020). Our findings suggest that hyperuricaemia at LN onset is an independent risk factor that predicts the development of CKD in patients with LN.

Reduced serum CTRP12 levels in type 2 diabetes are associated with renal dysfunction.

Serum C1q/TNF-related protein-12 (CTRP12) is one of the newly studied families of adipokines, which is believed to be associated with type 2 diabetes. However, the relationship between serum CTRP12 levels and diabetic nephropathy remains unclear. This study aimed to investigate the relationship between serum CTRP12 levels and renal function in patients with type 2 diabetes. A total of 115 type 2 diabetic patients and 54 healthy subjects were enrolled in this study. 52 patients with type 2 diabetes were in the diabetes group (T2DM). The 63 patients with renal dysfunction were diabetic nephropathy group (T2DM-DN) and were divided into microalbuminuria subgroup (31 cases) and macroalbuminuria subgroup (32 cases) according to the 24-h urine protein excretion rate. The concentrations of serum CTRP12 were determined by enzyme-linked immunosorbent assay. Serum CTRP12 level in T2DM and T2DM-DN groups was significantly lower compared with the control group, while CTRP12 level in T2DM-DN group was significantly lower than that in T2DM group, and was associated with the severity of renal insufficiency. After adjusting for gender and age, serum CTRP12 level was negatively correlated with the duration of diabetes, blood urea nitrogen (BUN), uric acid (UA) and 24-h urinary albumin excretion rate (UAE) in T2DM patients. Logistic regression analysis showed that serum CTRP12 level was significantly associated with renal dysfunction in type 2 diabetes mellitus. And the duration of diabetes, total cholesterol (CHOL) and neutrophils/lymphocytes (NLR) are independent risk factors for renal dysfunction in type 2 diabetes mellitus. Serum CTRP12 may be involved in the occurrence and development of diabetic nephropathy. Trial registration number and date of registration ChiCTR2000030794, March 14, 2020.

The Short-Term Renal Effects of Bariatric Surgery: A Comparative Study Between Sleeve Gastrectomy and One Anastomosis Gastric Bypass Operations Among Egyptian Patients With Severe Obesity

Obesity is a major health problem with many renal sequelae. Bariatric surgery (BS) has become the treatment of choice for severe obesity. This study was conducted to assess the short-term renal effects of BS and to compare such effects between two distinct forms of BS. A single-center non-randomized prospective observational study was conducted on 57 patients with severe obesity. Two distinct forms of BS have been performed; laparoscopic sleeve gastrectomy (LSG) and laparoscopic one anastomosis gastric bypass (OAGB). Anthropometric measurements, 24-h urinary creatinine clearance (CLCr), protein and oxalate excretion, and abdominal fat tissue analysis by computerized tomography were performed prior to surgery and 6months later. LSG and OAGB were performed in 47 and 10 participants, respectively. BS resulted in pronounced reduction of body mass index (- 27.1% ± 7.11), with no substantial weight loss discrepancy between LSG and OAGB. The median percent change in 24-h urinary CLCr and protein and oxalate excretion were - 35.7, - 42.2, and - 5.8, respectively. The median (IQR) percent change of urinary oxalate excretion was - 11.1 (- 22.6, - 1.4) and 113.08 (82.5, 179.7) for LSG and OAGB, respectively (p < 0.001). The subcutaneous abdominal fat surface area has been found to be the significant predictor of the persistence of glomerular hyperfiltration after BS. Both LSG and OAGB can alleviate many of the obesity-related pathological renal changes. However, postoperative hyperoxaluria remains a serious issue particularly in OAGB. Detailed radiological abdominal fat tissue analysis by CT may aid in predicting the renal outcome following BS.

Renal changes and estimation of glomerular filtration rate using different equations in morbidly obese Egyptian patients

Background and aimsObesity is a worldwide pandemic with multiple consequences including kidney affection. This study aimed to assess the effects of obesity on renal functions and to detect the most reliable formula of estimated glomerular filtration rate (eGFR) in morbidly obese patients. MethodsA cross-sectional, observational study was conducted on 82 morbidly obese patients. Anthropometric measurements were done for all patients and body adiposity (BAI) and visceral adiposity (VAI) indices were calculated after assessment of abdominal fat tissue analysis by computerized tomography (CT). Serum creatinine was incorporated into six different formulae of eGFR, then eGFR was compared with the 24-h measured creatinine clearance (CLcr) values. ResultsThe mean body mass index was 55.8 ± 9.5 kg/m2. Proteinuria and glomerular hyperfiltration (CLcr > 130 ml/min/1.73 m2) were detected in 68.3% and 91.5% of the patients, respectively. Cockcroft–Gault formula using total (CCG-TBW-eGFR) and adjusted body water (CCG-AjBW-eGFR) had the nearest values to measured CLCr. These two formulae had a moderate reliability and the lowest percentage of error (30% and 23%, respectively). Visceral and total abdominal fat tissue surface area and volume assessed by CT were directly correlated to the 24-h urinary protein excretion (r = 0.32, 0.24, 0.37 and 0.34, respectively; p = 0.02, 0.03, 0.004 and 0.002, respectively). ConclusionsGlomerular hyperfiltration and proteinuria are highly prevalent in morbidly obese patients. There is no ideal formula for GFR estimation in morbidly obese patients, however, TBW and AjBW incorporated into the Cockcroft–Gault can be helpful in those patients.

Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial

SGLT2 inhibition decreases albuminuria and reduces the risk of kidney disease progression in patients with type 2 diabetes. These benefits are unlikely to be mediated by improvements in glycaemic control alone. Therefore, we aimed to examine the kidney effects of the SGLT2 inhibitor dapagliflozin in patients with proteinuric kidney disease without diabetes. DIAMOND was a randomised, double-blind, placebo-controlled crossover trial done at six hospitals in Canada, Malaysia, and the Netherlands. Eligible participants were adult patients (aged 18-75 years) with chronic kidney disease, without a diagnosis of diabetes, with a 24-h urinary protein excretion greater than 500 mg and less than or equal to 3500 mg and an estimated glomerular filtration rate (eGFR) of at least 25 mL/min per 1·73 m2, and who were on stable renin-angiotensin system blockade. Participants were randomly assigned (1:1) to receive placebo and then dapagliflozin 10 mg per day or vice versa. Each treatment period lasted 6 weeks with a 6-week washout period in between. Participants, investigators, and study personnel were masked to assignment throughout the trial and analysis. The primary outcome was percentage change from baseline in 24-h proteinuria during dapagliflozin treatment relative to placebo. Secondary outcomes were changes in measured GFR (mGFR; via iohexol clearance), bodyweight, blood pressure, and concentrations of neurohormonal biomarkers. Analyses were done in accordance with the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT03190694. Between Nov 22, 2017, and April 5, 2019, 58 patients were screened, of whom 53 (mean age 51 years [SD 13]; 32% women) were randomly assigned (27 received dapagliflozin then placebo and 26 received placebo then dapagliflozin). One patient discontinued during the first treatment period. All patients were included in the analysis. Mean baseline mGFR was 58·3 mL/min per 1·73 m2 (SD 23), median proteinuria was 1110 mg per 24 h (IQR 730-1560), and mean HbA1c was 5·6% (SD 0·4). The difference in mean proteinuria change from baseline between dapagliflozin and placebo was 0·9% (95% CI -16·6 to 22·1; p=0·93). Compared with placebo, mGFR was changed with dapagliflozin treatment by -6·6 mL/min per 1·73 m2 (-9·0 to -4·2; p<0·0001) at week 6. This reduction was fully reversible within 6 weeks after dapagliflozin discontinuation. Compared with placebo, bodyweight was reduced by 1·5 kg (0·03-3·0; p=0·046) with dapagliflozin; changes in systolic and diastolic blood pressure and concentrations of neurohormonal biomarkers did not differ significantly between dapagliflozin and placebo treatment. The numbers of patients who had one or more adverse events during dapagliflozin treatment (17 [32%] of 53) and during placebo treatment (13 [25%] of 52) were similar. No hypoglycaemic events were reported and no deaths occurred. 6-week treatment with dapagliflozin did not affect proteinuria in patients with chronic kidney disease without diabetes, but did induce an acute and reversible decline in mGFR and a reduction in bodyweight. Long-term clinical trials are underway to determine whether SGLT2 inhibitors can safely reduce the rate of major clinical kidney outcomes in patients with chronic kidney disease with and without diabetes. AstraZeneca.

Effect of empagliflosin on renal filtration in patients with coronary heart disease undergoing percutaneous coronary intervention

Aim To evaluate the effect of empagliflozin on glycemia and renal filtration function in patients with stable ischemic heart disease (IHD) and type 2 diabetes mellitus (DM2) who underwent a percutaneous coronary intervention (PCI).Materials and methods This study included 40 patients with stable IHD and DM2 (age, 63 (58; 65) years; DM2 duration, 7 (4; 15) years) who had indications for an elective PCI. At baseline in the total sample, the level of glycated hemoglobin was 7.2 (6.5; 8.3)%; 48.7 % failed to achieve glycemic goals. A decrease in glomerular filtration rate (GFR) to below 60 ml/min/1.73 m2 was observed in 10.3 % of patients. All patients were divided into two group by simple randomization with successively assigned numbers. The main group consisted of 20 patients who received empagliflozin 10 mg/day in addition to their previous hypoglycemic therapy irrespective of their baseline glycemic control. Patients of the comparison group (n=20) continued on their previous hypoglycemic therapy as prescribed by their endocrinologist. The follow-up duration was 6 months. Statistical analysis was performed with the Statistica 10.0 software.Results The empagliflozin treatment improved the glycemic control; in the comparison group, no significant changes in glycemic control were observed. In both groups, GFR significantly decreased during the follow-up period; median decreases in GFR were -6.0 (-16.0; 4.0) and -8.4 (-26.5; 2.5) ml/min / 1.73 m2 in the main and comparison groups, respectively (p = 0.646). No significant changes in 24-h proteinuria were observed for patients taking empagliflozin. In the control group, the 24-h urinary protein excretion significantly progressed (p=0.011) during the follow-up period.Conclusion In patients with DM2 and stable IHD who underwent a PCI, addition of empagliflozin 10 mg/day to their current hypoglycemic therapy was associated with a significant improvement of glycemic control. The decrease in GFR during the empagliflozin treatment did not significantly differ from the value for patient receiving the other hypoglycemic therapy.

P0685RENAL SUBCAPSULAR ADIPOSE-DERIVED MESENCHYMAL STEM CELLS (ASC) ADMINISTRATION, ASSOCIATED TO LOSARTAN TREATMENT, PREVENTED THE PROGRESSION OF RENAL DAMAGE IN AN EXPERIMENTAL MODEL OF CHRONIC KIDNEY DISEASE (CKD)

Abstract INTRODUCTION / AIMS Chronic kidney disease (CKD) is considered a public health problem with epidemic proportions worldwide. Overactivity of the renin-angiotensin-aldosterone system (RAAS), associated to the establishment of a chronic self-sustained renal inflammation, are the main factors which contribute to the progression of CKD, leading to tissue fibrosis and loss of function. Consequently, RAAS inhibitors, such as the AT-1 receptor antagonist, Losartan, are among the most currently employed therapeutic strategies to slow down CKD progression, although the renoprotection afforded by these drugs is not complete. The association of anti-inflammatory and immunosuppressive drugs to RAAS inhibition is limited to the treatment of specific nephropathies, and its safety is still not entirely known. In this context, experimental application of mesenchymal stem cells (mSC) as a treatment to control renal inflammation and fibrosis have been showing promising results in studies with animal models of CKD. The aim of the present study was to analyze the renoprotective effects of subcapsular application of adipose-tissue derived mSC (ASC), associated to Losartan treatment, in rats submitted to 5/6 nephrectomy, after the establishment of CKD. METHODS ASC were isolated from gonadal adipose tissue from male Wistar rats, cultured until P4 and characterized by flow cytometry and in vitro differentiation. Male Wistar rats underwent 5/6 nephrectomy and were followed for 15 days to confirm the establishment of the nephropathy (CKD 15d). After this period, animals underwent a new surgery in which they received a subcapsular injection of 10 μL of sterile PBS (vehicle), or 2x106 ASC diluted in 10 μL of sterile PBS. Part of these animals were than treated orally with 50 mg/kg/day of Losartan (LOS) for further 15 days (groups CKD + LOS 30d and CKD + LOS + ASC 30d). A group of animals that received only subcapsular vehicle were kept untreated for the same period (CKD 30d). Sham-operated rats, euthanized at days 15 (Sham 15d) and 30 (Sham 30d), were used as controls. Survival rate, body weight (BW), systolic blood pressure (BP), 24h urinary protein (24h UPE) and albumin (24h UAE) excretion, serum creatinine (SCr) and blood urea nitrogen (BUN) concentrations, percentage (GS%) and index (GSI) of glomerulosclerosis, percentage of tubulointerstitial fibrosis (INT%) and renal infiltration by macrophages (CD68) were assessed 15 and 30 days after 5/6 nephrectomy. The obtained results are presented as Mean ± SE. Differences among groups were analyzed by one-way ANOVA. RESULTS The renal subcapsular application of ASC after the establishment of severe CKD improved the renoprotection obtained with the classic treatment with LOS. The association of LOS + ASC significantly improved animal’s survival, reduced blood pressure, proteinuria and albuminuria, prevented the development of glomerular structural damage and interstitial fibrosis, and inhibited renal inflammation by normalizing renal macrophage infiltration in the CKD + LOS + ASC group. CONCLUSIONS Our preliminary results demonstrate that the application of ASC, associated to the oral administration of LOS exerted additional renoprotection in the 5/6 renal ablation model, compared to LOS monotherapy. These findings suggest that ASC therapy could be employed as a therapeutic additive together with the traditional RAAS blockade, to detain the progression of CKD.

P0678RENAL SUBCAPSULAR ADMINISTRATION OF ADIPOSE DERIVED MESENCHYMAL STEM CELLS PREVENTED THE PROGRESSION OF RENAL DAMAGE IN AN EXPERIMENTAL MODEL OF CKD

Abstract INTRODUCTION / AIMS Chronic kidney disease (CKD) is a progressive, debilitating condition of high lethality, which prevalence have been increasing considerably in recent decades. CKD can be triggered by many different factors, such as genetic predisposition, systemic hypertension, diabetes mellitus and autoimmune diseases. It is characterized by the gradual loss of renal function, leading to kidney failure and the need for renal replacement therapy for the maintenance of life. Regardless of the etiology of CKD, the establishment of local renal inflammation, with leucocyte recruitment, cell proliferation, extracellular matrix accumulation, glomerular and tubulointerstitial fibrosis, contribute significantly to its establishment and evolution. Due to its known pathophysiology, the primary aim when clinically treating CKD is to slow the progression of renal function loss and the advance of inflammation. However, until the present moment, there is no efficient pharmacological treatment to completely arrest the aggravation of renal inflammation and, specially, renal fibrosis. This motivates the scientific community to develop experimental research in order to test new therapeutic approaches to stunt renal fibrosis. In this context, experimental application of mesenchymal stem cells (mSC) as a treatment to control renal inflammation have been showing promising results in studies with animal models of CKD. The aim of the present study was to analyze the renoprotective effects of subcapsular application of Adipose Tissue-derived mSC (ASC), in rats submitted to 5/6 nephrectomy, after the establishment of the disease (15 days after CKD induction), in order to more closely resemble the clinical settings in humans. METHODS ASC were obtained from gonadal adipose tissue from healthy male Wistar rats. These cells were cultured until P4 when characterization by flow cytometry and in vitro differentiation were performed. Male Wistar rats underwent 5/6 nephrectomy and were followed for 15 days until the complete establishment of CKD (group CKD 15d). At this time, animals underwent a new surgery in which they received a subcapsular injection of 2x106 ASC diluted in 10 μL of sterile PBS (group CKD + ASC 30d), or only 10 μL of sterile PBS (group CKD 30d). Sham-operated rats, euthanized at day 15 (Sham 15d) and 30 (Sham 30d) were used as controls. Survival rate, body weight (BW), 24h urinary protein (24h UPE) and albumin (24h UAE) excretion serum creatinine (SCr) and blood urea nitrogen (BUN) concentration, percentage (GS%) and index (GSI) of glomerulosclerosis, tubulointerstitial fibrosis (INT%) and renal infiltration by macrophages (CD68) were studied at 15 and 30 days after 5/6 nephrectomy. Our results are presented as Mean ± SE. Differences among groups were analyzed by one-way ANOVA. RESULTS ASC injection significantly improved the survival rate of CKD + ASC 30d animals, compared to the observed in the untreated group. Moreover, ASC treatment markedly reduced protein and albumin urinary excretion, prevented the development of glomerulosclerosis, both the percentage of sclerotic glomeruli and the index of glomerular damage, numerically reduced interstitial fibrosis and significantly avoided renal inflammation by halting the progression of renal cortical macrophage infiltration. CONCLUSIONS According to our results, subcapsular ASC application promoted considerable renoprotection in the 5/6 renal ablation model, even after the complete establishment of severe CKD, suggesting that experimental therapy with these cells could be associated to the current pharmacological treatments employed to detain the progression of CKD. Figure

Effects of Jian Pi Qu Shi Formula on intestinal bacterial flora in patients with idiopathic membranous nephropathy: A prospective randomized controlled trial

BackgroundThe incidence of idiopathic membranous nephropathy (IMN) has recently increased remarkably. Immune dysfunction caused by disordered intestinal flora might be an important factor affecting IMN. The Jian Pi Qu Shi Formula (JPQSF) shows promise in treating IMN. Here, we sequenced 16S rRNA genes to compare intestinal flora between patients with IMN and healthy persons. We also conducted a randomized controlled clinical trial to further compare the intestinal flora of patients with IMN treated with traditional Chinese medicine (TCM) and western medicine (WM). MethodsAmong 40 patients with IMN treated at Department of Nephrology in Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine between July 2016 and December 2018, we compared 30 of them with 10 healthy persons (controls). The IMN group was randomly assigned to receive JPQSF (TCM) or immunosuppressant WM therapy in (n = 15 per group) for 6 months. Intestinal microbiota diversity was analyzed using alpha diversity and beta diversity. Intestinal flora that significantly differed between the groups was analyzed using MetaStat. The effects and safety of the therapies were determined based on the values for plasma albumin, 24-h urine protein excretion, serum creatinine, urea nitrogen, estimate glomerular filtration rate (eGFR), complete blood count, and liver enzymes. All data were statistically analyzed using Statistical Package for the Social Sciences (SPSS) 20.0 statistical software. ResultsBaseline characteristics did not significantly differ between the IMN and healthy groups, or the TCM and WM groups. After six months of treatment, 24-h urinary protein significantly declined in the TCM and WM groups (before and after treatment: 3.24 ± 1.74 vs. 1.73 ± 1.85 g, P < 0.05 and 3.94 ± 1.05 vs. 1.91 ± 1.18 g, P < 0.05, respectively). Plasma albumin was significantly increased in the TCM group (before vs. after treatment: 32.44 ± 9.04 vs. 39.99 ± 7.03 g/L, P < 0.05), but did not significantly change in the WM group (31.55 ± 4.23 vs. 34.83 ± 9.14 g/L, P > 0.05). Values for urea nitrogen, serum creatinine, and eGFR did not significantly change in either group. The alpha diversity index for intestinal flora differed between the IMN and healthy groups, and the TCM and WM groups. Comparisons of multiple samples (beta diversity) revealed differences in intestinal flora between the IMN and healthy groups, and the TCM and WM groups. The Metastat analysis findings showed that the main genera that differed between the IMN group before treatment and the healthy group were Christensenellaceae_R-7_group, Bifidobacterium (77), Dorea, Escherichia-Shigella, Parabacteroides, Bifidobacterium, and Coprococcus_3. After TCM therapy, the main differential genera were Butyricimonas, Bacteroides, Alistipes, and Lachnospira, and after WM therapy, these were Ruminococcus_2, Lachnospiraceae_ND3007_group, Lachnospira, Bifidobacterium, Alistipes, and [Eubacterium]_ventriosum_group. ConclusionPatients with IMN might have disordered intestinal flora, and JPQSF can regulate intestinal flora in patients with IMN.

Double Negative B Cell Is Associated With Renal Impairment in Systemic Lupus Erythematosus and Acts as a Marker for Nephritis Remission.

Objective: Recent studies on double negative B cells (DN B cells) suggested that they have potential pathogenic roles in systemic lupus erythematosus (SLE). This study aimed to determine the circulating DN B cells in SLE patients and analyzed the clinical significance of this cell subset.Methods: Fifty-seven SLE patients and fifty healthy controls (HCs) were recruited in this study. Among the 57 SLE patients, 25 had lupus nephritis (LN). All patients were followed up for 24 weeks. Peripheral B cell subsets were analyzed by flow cytometry.Results: DN B cells were significantly elevated in the SLE patients, especially in the patients with LN (p < 0.01). DN B showed a positive correlation with 24-h urine protein excretion (24 h-UPE) levels (r = 0.444, p = 0.034) in LN patients, and inversely correlated with evaluated glomerular filtration rate (eGFR) (r = −0.351, p = 0.011). DN B cells had a positive correlation with plasma cells (r = 0.484, p < 0.001) and memory B cells (r = 0.703, p < 0.001). After treatment, decreased DN B cells were associated with LN alleviation (p = 0.002). In the follow-up, the remission rate of LN patients with decreased DN B cells was significantly higher than LN patients with increased DN B cells (83.33 vs. 25.00%, p = 0.030) at week 24.Conclusions: This study suggests that the peripheral DN B cells are positively correlated with the severity of renal damage in LN patients and may potentially be used as a prognostic marker in LN.

C3 glomerulopathy: experience of a pediatric nephrology center

ABSTRACT Background: C3 glomerulopathy (C3G) is an uncommon disease characterized by the deposition of complement factors in the glomeruli due to overactivation and dysregulation of the alternative pathway of complement. Objectives: This study aimed to describe the clinicopathological features, laboratory testing, clinical course, treatment, and outcomes of pediatric patients with C3G. Patients and Methods: We reviewed retrospectively the laboratory testing, kidney biopsy reports, and clinical features of 18 patients at our hospital from 2007 to 2019. Results: There were 18 cases, and the majority of the patients were girls (61.1%). The mean age at diagnosis was 11.3 ± 3.7 (5–17) years, and nephritic–nephrotic syndrome presentation in patients was more common (11 cases, 61.1%). Hematuria was found in 66.7% of the patients, of which the majority had microscopic hematuria (58.3%). Hypertension was observed in 10 (55.6%) patients. The mean glomerular filtration rate (eGFR) was 95.7 ± 47.3 mL/min/1.73 m2, and 24-h urinary protein excretion was 76.2 ± 48.6 mg/m2/h. Sixteen patients (88.9%) received renin–angiotensin–aldosterone system blockers (RASB), and two of them were taking RASB only. The majority of patients (83.3%) were treated with immunosuppressive therapy. Eculizumab was also given to one of them. At the last follow-up, two patients had levels of less than 60 mL/min/1.73 m2 for eGFR. Seven patients with immunosuppressive treatment achieved complete remission. Conclusion: C3G shows a variable clinical presentation and response to immunosuppressive therapy. In the present study, we observed that the most common presentation was nephritic and/or nephrotic syndrome and partially responded to treatment to RASB and immunosuppressants.

Network Meta-analysis of Four Chinese Patent Medicines Combined with Angiotensin Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Early Diabetic Nephropathy Treatment

The objective of the study is to systematically evaluate the efficacy of four Chinese patent medicines in combination with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in the treatment of early diabetic nephropathy (DN). Retrospectively, previously published randomized controlled trials (RCTs) of four different Chinese patent medicines combined with ACEI or ARB in the treatment of patients with early DN were searched overall from databases. The data were analyzed by R, Generate Mixed Treatment Comparisons and STATA softwares. A total of 78 RCTs were finally included. Network meta-analysis showed that the total effective rate of the Jinshuibao capsule-ACEI/ARB combination group and Huangkui capsule-ACEI/ARB combination groups were better than the others; Jinshuibao capsule-ACEI/ARB combination group reduced the 24-h urinary protein excretion (24-h UTP), urine microalbumin excretion rate (UAER), serum creatinine (Scr), and glycosylated hemoglobin (HbAlc) values. The Huangkui capsule-ACEI/ARB combination demonstrated a better reduction of (blood urea nitrogen [BUN]). Reduced incidences of adverse effects were only observed on treatment with Bailing capsule-ACEI/ARB combination. In early DN, combination of Jinshuibao capsule-ACEI/ARB provided the highest effective rate; moreover, it could reduce the 24-h values of UTP, UAER, Scr, and HbAlc; Huangkuai capsule-ACI/ARB combination group showed a good effect on reducing BUN. Bailing capsule-ACEI/ARB combination group had reduced the incidences of adverse reactions.

Efficacy of entecavir in treating hepatitis B virus-associated membranous nephropathy.

hepatitis B virus-associated membranous nephropathy (HBV-MN) is the most common pathological type of hepatitis B virus-associated glomerulonephritis. This study evaluated the efficacy of entecavir antiviral therapy for HBV-MN patients due to the intolerable side effects of interferon-alpha and high incidence rate of drug-resistance in lamivudine therapy. thirty-two patients with HBV-MN were identified by biopsy and treated with entecavir for 52 weeks. These patients were followed up to evaluate outcomes of entecavir-treatment. Descriptive statistics were used to summarize patient demographics and treatment outcomes. entecavir treatment reduced 24-h urinary protein excretion. The total probability of partial proteinuria and complete remission at 24 and 52 weeks was 53.1 and 78.1 %, respectively. A decrease of circulating HBV-DNA was observed in all patients with active HBV replication. The significant decrease of 24-h urinary protein began at 12 weeks, as early as the decrease of serum HBV-DNA level. The serum HBV DNA titers at baseline and after 52 weeks of treatment were 4.3 ± 2.8 log10 and 2.3 ± 1.7 log10, respectively. Meanwhile, eGFR increased from 100.3 ± 20.5 ml/min/1.73 m2 at baseline to 107.7 ± 15.9 ml/min/1.73 m2 after 52 weeks of treatment. The serum alanine aminotransferase level (ALT) gradually decreased to normal during entecavir antiviral treatment. entecavir treatment in HBV-MN patients was carefully described. Complete remission and HBV replication suppression were induced by entecavir treatment in HBV-MN patients. Patients with high serum creatinine (Scr), ALT and low eGFR levels benefit more from entecavir treatment. Entecavir therapy is well tolerated by patients and no adverse reactions were observed.

Evaluation of the efficacy and safety of TWHF in diabetic nephropathy patients with overt proteinuria and normal eGFR

The aim of this study was to evaluate the efficacy and safety of Tripterygium Wilfordii Hook F (TWHF) in DN patients with overt proteinuria and normal eGFR. 124 eligible DN patients were randomly assigned into two groups to receive either valsartan 160mg/d treatment (control group) or TWHF 60mg/d plus valsartan 160mg/d treatments (TWHF group) for 24 weeks. The changes of clinical, biochemical data and adverse events during observation period were all analyzed. The primary endpoint was a reduction in 24-h urine protein excretion between baseline and the end of study, the secondary endpoint was to observe the change in estimated glomerular filtration rate (eGFR) between two groups. After treatment, there was a more significant decrease in proteinuria in patients who received TWHF treatment (from 4.95±1.27g/24h to 3.36±0.83g/24h) compared to valsartan monotherapy (from 5.21±1.59g/24h to 4.52±1.06g/24h). The percentage change in urine protein excretion was -32.12% in TWHF group and -13.24% in valsartan group. Patients' plasma albumin in TWHF group (from 32.53±5.24g/L to 36.91±4.42g/L) was higher than that in control group (from 33.18±4.87g/L to 34.67±4.75g/L). No significant change in blood pressure, blood glucose, eGFR, and serum potassium was observed. But the adverse events in TWHF group were higher than those in control group. TWHF is more effective than valsartan monotherapy in reduction of proteinuria in DN patients with overt proteinuria and normal eGFR, but with more adverse effects.

Spot Urinary Albumin-to-Creatinine Ratio: A Novel Marker for Detecting Fetomaternal Outcomes and Complications in Preeclamptic Women.

Preeclampsia is a multisystem endothelial disease leading to glomeruloendotheliosis with endothelial leak causing significant proteinuria. It is associated with high maternal and fetal risks and fetomaternal morbidity and mortality. Spot urinary albumin-to-creatinine ratio (ACR) leads to earlier detection of glomerular damage leading to prompt management of preeclamptic patients. To study the correlation between fetomaternal outcomes of preeclamptic patients with spot urinary ACR. Spot urinary ACR was measured in 70 consecutive patients with preeclampsia in Assam Medical College, Dibrugarh. The best cutoff value to differentiate between significant and insignificant proteinuria was calculated. Mean spot urinary ACR was calculated in all maternal outcomes (mode of onset of labor and mode of delivery), and maternal complications (elevated liver enzymes, renal insufficiency, severe hypertension, coagulation disturbances and thrombocytopenia, antepartum and postpartum hemorrhage) and fetal complications and outcomes (birth weight, Apgar score, IUGR, need for resuscitation, NICU requirement, neonatal sepsis, jaundice and mortality) and the correlation were studied. The best cutoff value to differentiate significant and insignificant proteinuria was calculated as 291.9mg/g beyond which adverse fetomaternal outcomes and complications were seen. All maternal and fetal outcomes and complications had high mean spot urinary ACR and were found to be significant (p < 0.05). Mode of delivery and birth weight of babies showed no statistical significance though low-birth-weight babies had high mean spot ACR. Compared with 24-h urinary protein excretion, spot urinary ACR is a simple and accurate indicator of significant proteinuria and helps to detect fetomaternal outcomes in preeclamptic women which may lead to prompt management to reduce fetomaternal complications.

Accuracy of the 24-h urine protein excretion value in patients with preeclampsia: correlation with instant and 24-h urine protein/creatinine and albumin/creatinine ratios

The aim of this study was to determine the accuracy of the 24-h urine collection in preeclamptic pregnant women. This study included 65 singletons with preeclampsia and 53 singleton patients in a control-matched group. The ratio of inaccurate 24-h urine collection was measured by calculating expected urine creatinine excretion according to the proportion of pre-pregnancy weight and the lean body mass (LBM) of the patients. Comparisons were made between the accurately-collected 24-h urine protein excretion rates and the instant and 24-h urine protein/creatinine (P/Cr) and albumin/creatinine (A/Cr) ratios. Twenty-four-hour urine collection used to diagnose patients with preeclampsia was incorrectly collected 15–73.5% of the time among the patients and the control group. Instant and 24-h urine P/Cr and A/Cr ratios were correlated with total 24-h proteinuria among the patients in whom urine was collected correctly. Considering the 24-h urine P/Cr ratio, rather than the 24-h urine protein excretion value, is a better way to diagnose preeclampsia.IMPACT STATEMENTWhat is already known on this subject? Twenty-four-hour urine collection is considered as the gold standard of diagnosing proteinuria in preeclampsia, in case of the correctly collected.What do the results of this study add? Generally, in the literature the correctness of 24-h proteinuria is not questioned. However, it is actually quite important in daily practice to make the correct diagnosis of the proteinuria not to misdiagnose preeclampsia.What are the implications of these findings for clinical practice and/or further research? In this article, we aimed to show the importance of accurately collected 24-h urine in preeclampsia. We consider and advise to change the gold standard of this technique to 24-h protein/creatinine (P/Cr) ratio, in order to make correct diagnosis of the preeclampsia.

Effect of Platelet Rich Plasma on an Experimental Rat Model of Adriamycin Induced Chronic Kidney Disease

AbstractBackground: Chronic kidney disease (CKD) is a world-wide health problem with increased mortality and morbidity. Currently, there is no effective protective therapy against CKD- induced renal damage with its sequel of end stage renal disease. Platelet-rich plasma (PRP) has a progressively gained consideration in wound healing, repair/regeneration of damaged tissues and conservation of organ function.Aim of Study: This current study was planned to evaluate the possible protective effect of PRP treatment on a rat model of Adriamycin (ADR)-induced CKD.Material and Methods: Sixty male albino rats were in-cluded; 30 were used for PRP preparation and the other 30, were randomly categorized into three equal groups of ten rat each: Normal control group, ADR group and PRP treated ADR group. At the end of experimental regimen (6 weeks), 24h urine samples were collected for measuring 24h urinary protein excretion and creatinine clearance (Cr Cl), then rats were decapitated and blood samples were collected for meas-uring serum albumin, triglycerides and cholesterol along with serum creatinine and blood urea nitrogen (BUN). Renal tissue samples were harvested and used for determination of renal level and mRNA expression of nephrin along with levels of hepatocyte growth factor (HGF), malondialdehyde (MDA), super oxide dismutase (SOD) activity, tumor necrosis factor alpha (TNF-a), interleukin 1-b (IL-1b), and transforming growth factor 1b (TGF 1b) in renal homogenates.Results: Platelet rich plasma treatment improved ADR induced proteinuria, hyperlipidemia and renal dysfunction, which was accompanied by parallel upregulation of renal nephrin and inhanced levels of HGF and SOD activity, whereas the increased levels of TNF-a, IL-1b and TGF 1b were attenuated.Conclusion: Platelet rich plasma could potentially protect against ADR induced CKD by alleviating its associated proteinuria, hyperlipidemia and the altered oxidative stress, inflammatory and fibrogenic responses.