Urinary Total Protein Excretion Research Articles

Atrasentan in Patients with IgA Nephropathy.

Patients with IgA nephropathy and severe proteinuria have a high lifetime risk of kidney failure. The efficacy and safety of the selective endothelin type A receptor antagonist atrasentan in reducing proteinuria in patients with IgA nephropathy are incompletely understood. We are conducting a phase 3, multinational, double-blind, randomized, controlled trial involving adults with biopsy-proven IgA nephropathy, a total urinary protein excretion of at least 1 g per day, and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. Patients were randomly assigned to receive atrasentan (0.75 mg per day) or matched placebo for 132 weeks. The primary outcome, assessed at a prespecified interim analysis of data from the first 270 patients in the main stratum, was the change in the 24-hour urinary protein-to-creatinine ratio from baseline to week 36; the change was estimated with the use of a repeated-measures model. (An exploratory stratum of patients who were receiving a sodium-glucose cotransporter 2 inhibitor were included in a separate analysis.) Safety analyses were based on adverse events across the entire main stratum. A total of 340 patients were recruited into the main stratum. Among the first 270 patients in the main stratum (135 per trial group) who completed the week 36 visit, the geometric mean percentage change in the urinary protein-to-creatinine ratio relative to baseline was significantly greater with atrasentan (-38.1%) than with placebo (-3.1%), with a geometric mean between-group difference of -36.1 percentage points (95% confidence interval, -44.6 to -26.4; P<0.001). The percentage of patients with adverse events did not differ substantially between the two groups. Fluid retention was reported by 19 of 169 patients (11.2%) in the atrasentan group and in 14 of 170 (8.2%) in the placebo group but did not lead to discontinuation of the trial regimen. No apparent cases of cardiac failure or severe edema occurred. In this prespecified interim analysis, atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo in patients with IgA nephropathy. (Funded by Novartis; ALIGN ClinicalTrials.gov number, NCT04573478.).

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.

Long-Term Effects of Suramin on Renal Function in Streptozotocin-Induced Diabetes in Rats.

In short-term diabetes (3 weeks), suramin, a drug used clinically, affects renal function and the expression of vascular endothelial growth factor A (VEGF-A), which may be involved in the pathogenesis of diabetic nephropathy, the main cause of end-stage renal disease. In the present study, we evaluated the long-term (11 weeks) effects of suramin (10 mg/kg, i.p., once-weekly) in diabetic rats. Concentrations of VEGF-A, albumin, soluble adhesive molecules (sICAM-1, sVCAM-1), nucleosomes, and thrombin-antithrombin complex (TAT) were measured by ELISA, total protein was measured using a biuret reagent. Glomerular expression of VEGF-A was evaluated by Western blot, mRNA for VEGF-A receptors in the renal cortex by RT-PCR. The vasoreactivity of the interlobar arteries to acetylcholine was assessed by wire myography. Long-term diabetes led to an increased concentration of VEGF-A, TAT, and urinary excretion of total protein and albumin, and a decrease in the concentration of sVCAM-1. We have shown that suramin in diabetes reduces total urinary protein excretion and restores the relaxing properties of acetylcholine relaxation properties to non-diabetic levels. Suramin had no effect on glomerular expression VEGF-A expression and specific receptors, and on sICAM-1 and nucleosomes concentrations in diabetic rats. In conclusion, the long-term effect of suramin on the kidneys in diabetes, expressed in the reduction of proteinuria and the restoration of endothelium-dependent relaxation of the renal arteries, can be considered as potentially contributing to the reduction/slowing down of the development of diabetic nephropathy.

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

Nephroprotective and antilithiatic activities of Costus spicatus (Jacq.) Sw.: Ethnopharmacological investigation of a species from the Dourados region, Mato Grosso do Sul State, Brazil

Ethnopharmacological relevanceCostus spicatus (Jacq.) Sw., also known as “cana-do-brejo,” is a species that is widely used in Brazilian traditional medicine for the treatment of kidney diseases. However, no studies have evaluated its nephroprotective and antilithiatic effects. AimTo investigate nephroprotective and antilithiatic effects of C. spicatus in a preclinical model of acute kidney injury (AKI) and in vitro nephrolithiasis. Materials and methodsC. spicatus leaves were collected directly from the natural environment in the Dourados region, Mato Grosso do Sul State, Brazil. The ethanol-soluble fraction of C. spicatus (ESCS) was obtained by infusion. Phytochemical characterization was performed by liquid chromatography coupled to diode array detector and mass spectrometer (LC-DAD-MS). We assessed whether ESCS has acute or prolonged diuretic activity. The nephroprotective effects of ESCS were evaluated in a model of AKI that was induced by glycerol (10 ml/kg, intramuscularly) in Wistar rats. Different doses of ESCS (30, 100, and 300 mg/kg) were administered orally for 5 days before the induction of AKI. Urinary parameters were measured on days 1, 3, 5, and 7. Twenty-four hours after the last urine collection, blood samples were obtained for the biochemical analysis. Blood pressure levels, renal vascular reactivity, renal tissue redox status, and histopathological changes were measured. Antilithiatic effects were evaluated by in vitro crystallization. Calcium oxalate precipitation was induced by sodium oxalate in urine samples with ESCS at 0.05, 0.5, and 5 mg/ml. ResultsFrom LC-DAD-MS analyses, flavonoids, saponins and other phenolic compounds were determined in the composition of ESCS. Significant reductions of the excretion of urinary total protein, creatinine, sodium, and potassium were observed in the AKI group, with significant histopathological damage (swelling, vacuolization, necrosis, and inflammatory infiltration) in the proximal convoluted tubule. Treatment with ESCS exerted a significant nephroprotective effect by increasing the urinary excretion of total protein, urea, creatinine, sodium, potassium, calcium, and chloride. All of the groups that were treated with ESCS exhibited a reduction of histopathological lesions and significant modulation of the tissue redox state. We also observed a concentration-dependent effect of ESCS on the crystallization of urinary crystals, with reductions of the size and proportion of monohydrated crystals. ConclusionThe data suggest that C. spicatus has nephroprotective and antilithiatic effects, suggesting possible effectiveness in its traditional use.

Abstract MP44: Proteolytic Activation Of ENaC Mediates Fructose-Induced Salt-Sensitive Hypertension

In nephrotic syndrome, glomerular injury leads to filtration of plasma proteases. Once in the urine, these enzymes cleave and activate the epithelial Na channel (ENaC) causing inappropriate Na retention and hypertension. Dietary fructose causes inappropriate Na retention and salt-sensitive hypertension but whether proteolytic activation of ENaC is involved, and the source of the proteases, is unknown. We hypothesized that dietary fructose increases expression and release of proteases from the proximal nephron, and that these enzymes activate ENaC thereby causing Na retention and salt-sensitive hypertension. To test this hypothesis we first measured proximal nephron protease expression and urinary protease excretion in rats on either a high-salt diet without fructose (high salt) or one containing 4% NaCl plus 20% fructose in the drinking water (high salt/fructose) for 7 days. High salt/fructose treatment increased proximal nephron expression of trypsin I, an enzyme known to cleave and activate ENaC, by 68±7% (p &lt; 0.01). Urinary excretion of trypsin I was 8.4±1.3 arbitrary units/μg protein in rats fed high salt while it was 20.3±4.6 arbitrary units/μg protein in those on the high salt/fructose diet, 142% greater (p &lt; 0.02). There was no difference in total urinary protein excretion between groups. Finally, we examined the effect of high salt/fructose and high salt plus 20% glucose) high salt/glucose) on blood pressure before and after oral amiloride. After 7 days the systolic blood pressure of rats on high salt/fructose was 148±6 mm Hg while it was only 124±5 in those on high salt/glucose (p &lt; 0.02). Amiloride reduced systolic blood pressure in rats on the high salt/fructose diet from 148±6 to 134±5 mm Hg but had no significant effect on the high salt/glucose group. We conclude that proteolytic cleavage of ENaC contributes to fructose-induced salt-sensitive hypertension and that the source of the protease(s) is likely the proximal tubule rather than glomerular filtration.

Proteolytic Activation of ENaC Mediates Fructose‐Induced Salt‐Sensitive Hypertension

Proteolytic cleavage of the amiloride‐sensitive epithelial sodium channel (ENaC) by serine proteases such as trypsin leads to channel activation. In nephrotic syndrome, glomerular injury allows filtration of such enzymes causing ENaC‐dependent Na retention and hypertension(PMID: 23216619). Dietary fructose also causes Na retention and salt‐sensitive hypertension at least, in part, via altered hormonal signaling and metabolism in the proximal nephron. Proximal tubules normally secrete proteases into the forming urine but whether they are a source of proteases that cleave and activate ENaC in fructose‐induced salt‐sensitive hypertension is unknown. We hypothesized that dietary fructose increases expression and release of proteases from the proximal nephron, and that these enzymes activate ENaC thereby causing Na retention and salt‐sensitive hypertension. To test this hypothesis we first measured proximal nephron protease expression and urinary protease excretion in rats on either a high‐salt diet containing 4% NaCl without fructose (high salt) or one containing high salt plus 20% fructose in the drinking water (high salt/fructose) for 7 days. High salt/fructose treatment increased proximal nephron expression of trypsin I, an enzyme known to cleave and activate ENaC, by 70% (p &lt; 0.01) compared to high salt alone. Urinary excretion of trypsin I was 8.4±1.3 arbitrary units/μg protein in rats fed high salt while it was 20.3±4.6 arbitrary units/μg protein in those on the high salt/fructose diet, 142% greater (p &lt; 0.02). There was no difference in total urinary protein excretion between groups. Finally, we examined the effect of high salt/fructose and high salt plus 20% glucose (high salt/glucose) on blood pressure before and after oral amiloride. After 7 days, the systolic blood pressure of rats on high salt/fructose was 142±6 mm Hg while it was only 121±6 mm Hg in those on high salt/glucose (p &lt; 0.05). After 10 days, the systolic blood pressure of rats on high salt/fructose was 148±6 mm Hg while it was only 124±5 in those on high salt/glucose (p &lt; 0.02). Amiloride treatment for 24 hrs reduced systolic blood pressure in rats on the high salt/fructose diet from 148±6 to 134±5 mm Hg but did not decrease it in the high salt/glucose group. We conclude that proteolytic cleavage of ENaC contributes to fructose‐induced salt‐sensitive hypertension and that the source of the protease(s) is likely the proximal tubule rather than glomerular filtration.Support or Funding InformationNLHBI HL128053

AMELIORATION OF GENTAMICIN-INDUCED RENAL DAMAGE IN RATS BY ETHANOL EXTRACT OF THE WHOLE PLANT BIOPHYTUM SENSITIVUM (LINN.) DC

Objective: Present study was undertaken to investigate the nephroprotective activity of whole plant ethanol extract of Biophytum sensitivum Linn. DC (B. sensitivum; EEBS) on gentamicin induced-nephrotoxicity in Wistar albino rats.Methods: Animals were divided into five groups, containing six animals in each. Gentamicin (GM) 100 mg/kg/d; i. p., was given to all groups except normal control to induce nephrotoxicity for a period of 8 d in rats. Animals in Group I served as control and Group II as GM-treated or nephrotoxic control. Group III received standard quercetin (50 mg/kg; p. o.); group IV received EEBS (250 mg/kg; p. o.) and group V received EEBS (500 mg/kg; p. o.), for 8 d. Several renal functional tests and injury markers such as a change in body weight, water intake, urine volume and pH, urinary levels of total protein, albumin, sodium, potassium, calcium and magnesium were measured. Different hematological parameters including, red blood cells (RBC), hemoglobin (Hb), packed cell volume (PCV), mean corpuscular haemoglobin (MCH), white blood corpuscles (WBC), lymphocyte, monocyte, polymorphs and eosinophil were also analyzed.Results: The results revealed that co-administration of EEBS at 250 and 500 mg/kg significantly reduced the urinary excretion of total protein (4.05±0.04, 3.53±0.05 g/dl), albumin (0.81±0.08, 0.71±0.00 g/dl), calcium (8.05±0.05, 7.81±0.06 mg/dl) and magnesium (0.79±0.05, 0.77±0.06 mg/dl) respectively. EEBS treatment in group IV and V animals produced a significant increase in body weight (2.58±0.17, 2.52±0.22 g), water intake (17.35±0.82, 17.87±0.86 ml/24 h) urine output (7.24±0.15, 7.88±0.08 ml/24 h), compared to animals in group II. Co-therapy with both doses of extracts also showed significant increase in RBC (6.85±0.31, 7.10±0.43 million/mm3) Hb (13.96±0.21, 13.83±0.31 g/dl), MCH (20.45±0.49, 20.67±0.51 pg) and PCV (38.29±0.42, 38.53±0.20%) levels, whereas WBC (8.24±0.21, 8.15±0.10 1X103/mm3) and polymorphs (14.19±0.20, 14.05±0.11%) levels were found to be significantly reduced respectively in animals than those in toxic control group.Conclusion: This study substantiated and confirmed the ethnomedical usefulness of B. sensitivum as a nephroprotective and antioxidant agent.

Lime powder treatment reduces urinary excretion of total protein and transferrin but increases uromodulin excretion in patients with urolithiasis.

Our previous study has shown that lime powder (LP) had an inhibitory effect against calcium oxalate stone formation. However, the precise mechanisms underlying such beneficial effect remained unclear. Our present study thus aimed to address the effect of LP on excretory level and compositions of urinary proteins using a proteomics approach. From a total of 80 calcium oxalate stone formers recruited into our 2-year randomized clinical trial of LP effect, 10 patients with comparable age and clinical parameters were selected for this proteomic study. 24-h urine specimens were collected from all subjects, at baseline (before) and after LP treatment for 6months, and then subjected to quantitative proteomics analysis and subsequent validation by ELISA. Total urinary protein excretion was significantly decreased by LP treatment, but unaffected by placebo. Nanoflow liquid chromatography coupled to tandem mass spectrometry (nanoLC-MS/MS) followed by quantitative analysis revealed 17 proteins whose levels were significantly altered (16 decreased and 1 increased) exclusively by LP treatment. Among these, the decrease of transferrin and increase of uromodulin were validated by ELISA. Moreover, there was a significant correlation between microalbuminuria and urinary transferrin level by Pearson's correlation test. In summary, LP treatment caused significant reduction in total urinary protein excretion and changes in urinary protein compositions that could be linked to stone inhibitory effects and might be relevant mechanisms responsible for the beneficial effects of LP to prevent kidney stone formation and recurrence.

Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice

Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium (137Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation (137Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137Cs). Further investigations are required to clarify the mechanisms involved in the internal IR-induced nephrotoxicity.

Nephroprotective effect of ethanol extract of Biophytum sensitivum (Linn.) DC in cisplatin-induced experimental renal damage in rats

The present study was undertaken to investigate the nephroprotective and antioxidant activity of whole plant ethanol extract of Biophytum sensitivum Linn. DC (B. sensitivum; EEBS) in cisplatin induced-nephrotoxicity in Wistar albinorats. Animals were divided into five groups, containing six animals in each. A single dose of cisplatin (CDDP)8 mg/kg/day; i.p.was given to all groups on fifth day except normal control to induce nephrotoxicity in rats. Animals in Group I served as control, received 1 ml saline solution/day; i.p., for 9 days and Group II as CDDP-treated or nephrotoxic control. Group III received standard quercetin (50 mg/kg/day; p.o.); group IV received EEBS (250 mg/kg/day; p.o.) and Group V received EEBS (500 mg/kg/day; p.o.), for nine days. Several renal functional tests and injury markers such as body weight, water intake, urine volume and pH, urinary levels of total protein, sodium, potassium, calcium and magnesium were measured. Serum levels of blood urea nitrogen (BUN), uric acid, creatinine, total protein, sodium, potassium, calcium and magnesium were determined. Antioxidant enzyme activities were also analyzed. The results revealed that co-administration of EEBS significantly reduced the urinary excretion of total protein and calcium. Serum concentration of BUN and creatinine were significantly lowered by treatment with EEBS. EEBS treatment produced significant increase in body weight, urine pH, and serum levels of total protein, calcium, sodium and antioxidant enzyme activities, compared to animals in group II. Hence, this study substantiated and confirmed the ethno-medical usefulness of B. sensitivum as nephroprotective and antioxidant agent.

ALLEVIATION OF CISPLATIN INDUCED NEPHROTOXICITY IN ALBINO RATS BY ROOTS OF Catunaregam uliginosa

ABSTRACT:Objective: To evaluate the nephroprotective effect of ethanolic extract of roots of Catunaregam ulginosa in cisplatin induced nephrotoxicity in albino rats.Methodology: Ethanolic extract was prepared by hot extraction method and subjected to preliminary phytochemical studies. Based on acute toxicity studies nephroprotector was screened at two dose levels i.e., 200mg/kg bd wt and 400 mg/kg bd wt in both curative and prophylactic regimens. Cisplatin at a dose of 5mg/kg bd. wt was given intraperitoneally to induce nephrotoxicity. Nephroprotector activity was assessed by determining blood urea nitrogen (BUN), serum creatinine(SC), urinary total protein(UTP) and creatinine clearance. Antioxidant enzymes like super oxide dismutase (SOD), catalase (CAT), glutatathione reduced (GSH) activities and lipid peroxidation (LPO) levels were determined in renal tissue. Histological studies had been carried per se.Results: Animals which received cisplatin exhibited significant increase in serum marker levels, increased urinary total protein excretion and reduced creatinine clearance. Further significant decrease in GSH, SOD, CAT and increase in LPO levels was observed. Ethanolic extract of roots of Catunaregam ulginosa reversed the effects induced by cisplatin in dose dependent manner in both curative and prophylactic regimens. Histological studies substantianed the above results.Conclusion: The findings of the present study support the alleviation of cisplatin induced nephrotoxicity by the ethanolic extract of roots of Catunaregam ulginosa and thus validate its ethnomedicinal use.Key words: Catunaregam ulginosa, Cisplatin, Nephrotoxicity, Lipid peroxidation

Tacrolimus combined with low-dose corticosteroids is an effective and safe therapeutic option for refractory IgA nephropathy.

Tacrolimus (TAC) has been shown to improve remission from proteinuria in patients with refractory IgA nephropathy (IgAN); however, the efficacy and safety of TAC in such patients have not been fully explored. Therefore, the present study was conducted to evaluate the tolerance to and efficacy of TAC combined with low-dose corticosteroids in patients with refractory IgAN. This was a single-center retrospective study. A total of 28 patients with refractory IgAN were randomly included and received TAC plus corticosteroid; 26 patients received TAC and prednisone, and 2 patients received TAC and methylprednisolone. In addition, all patients were treated with an angiotensin inhibitor. Total urinary protein excretion, serum albumin, blood glucose, complete remission (CR), partial remission (PR), cholesterol, low-density lipoprotein (LDL), serum creatinine (Scr) and estimated GFR (eGFR) were tested at baseline and at 3, 6 and 12 months after the initiation of treatment in all patients. The primary endpoints were CR and PR. Secondary endpoints included changes of Scr, eGFR, clinical data and adverse events. After 12 months, CR was achieved in 40.1% of patients and PR in 43.4%, yielding a total response rate of 83.5%, and the total urinary protein excretion, serum albumin, cholesterol and LDL results were improved significantly compared with those at baseline. Proteinuria and serum albumin results were significantly improved by month 3 of treatment. Two patients relapsed during months 3-6 of follow-up. At the 12-month follow-up, renal function was improved compared with the baseline level as evidenced by eGFR and Scr, respectively. The blood glucose level was stable. One case of pneumococcal pneumonia developed in a patient treated with TAC plus low-dose methylprednisolone and one case of upper gastrointestinal hemorrhage was found in a patient treated with TAC plus low-dose prednisone; both cases completely recovered after treatment. In conclusion, TAC combined with low-dose corticosteroids may be an effective and safe therapeutic option for the treatment of refractory IgAN. However, given the small number of patients in this study, further prospective randomized controlled trials are required with a larger sample of participants and longer follow-up period.

Preeclampsia in the rat: validation of the deoxycorticosterone (DOCA)‐salt model

Preeclampsia (PE) is a multi‐system disorder that typically occurs during the second and third trimesters of pregnancy. PE complicates 7–10% of all pregnancies worldwide and is a major cause of fetal and maternal morbidity and mortality. The hallmarks of PE include pregnancy induced‐hypertension (PIH), proteinuria, reduction in renal function, intrauterine growth restriction (IUGR) of the fetus, chronic immune activation, and multi‐organ dysfunction. The pathology of PE is not well understood. In the present study, DOCA‐salt treatment was validated as a model of PE in the female (F) Sprague‐Dawley rat. Normal pregnant (NP) and DOCA‐salt treated pregnant (DSP) F rats were studied, using time release DOCA‐impregnated silicone rubber implants (200 mg/kg) and saline drinking water (1% NaCl/0.2% KCl) from the onset of pregnancy until term. At term (day 18–20 of pregnancy), systolic blood pressure (tail cuff method) was elevated in DSP (146 ± 2 mmHg) vs. NP (115 ± 1 mmHg). In DSP, total urinary protein excretion was measurably higher in DSP (29.67 ± 11 mg/day) compared to NP (14.25 ± 10 mg/day). In addition, fetal weight was lower in DSP (2.52 ± 0.09 g) than in NP (4.05 ± 0.34 g), and maternal body weight was higher in NP (388 ± 5 g) compared to DSP (355 ± 25 g). These data suggest that DOCA‐salt treatment creates an accurate model of PIH and PE in the F rat.Support or Funding Information(State of Texas)

Antiurolithiatic activity of Abelmoschus moschatus seed extracts against zinc disc implantation-induced urolithiasis in rats.

Background:The commonly used techniques for removing renal calculi are associated with the risk of acute renal injury and increase in stone recurrence which indicates an urgent need for alternate therapy.Objectives:The aim was to evaluate the antiurolithiatic activity of Abelmoschus moschatus seed extracts in rats.Materials and Methods:Urolithiasis was induced by surgical implantations of zinc disc in the urinary bladders of rats. Upon postsurgical recovery, different doses of chloroform (CAM) and methanolic (MAM) extracts of A. moschatus seeds (viz., 100, 200 and 400 mg/kg body weight) were administered to disc implanted rats for the period of 7 days by the oral route. Antiurolithiatic activity was evaluated by measuring various dimensions of stones and estimating levels of various biomarkers in serum and urine samples.Results:A significant decrease in urinary output was observed in disc implanted animals, which was prevented by the treatment with extracts. Supplementation with extracts caused significant improvement in glomerular filtration rate and urinary total protein excretion. The elevated levels of serum creatinine, uric acid, and blood urea nitrogen were also prevented by the extracts. The extracts significantly reduced deposition of calculi deposition around the implanted disc. This antiurolithiatic potential is observed at all doses (100, 200, and 400 mg/kg) of MAM, whereas only higher dose (400 mg/kg) of CAM showed significant antiurolithiatic potential.Conclusion:The extracts of A. moschatus seeds possessed significant antiurolithiatic activity. The possible mechanism underlying this effect is mediated collectively through diuretic, antioxidant, and free-radical scavenging effects of the plant.

Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules.

Protective effect of standardized extract of Biophytum sensitivum against calcium oxalate urolithiasis in rats

ObjectiveThe present study investigated the antiurolithiatic effect of standardized methanolic extract of Biophytum sensitivum (MBS) against calcium oxalate urolithiasis in rats. MethodsThe MBS was standardized for amentoflavone content by HPLC method. Calcium oxalate urolithiasis was induced in rats by ethylene glycol–ammonium chloride feeding in drinking water. Antiurolithiatic activity of MBS was evaluated at three doses (100, 200 and 400mg/kg) in curative and preventive regimen by estimating histological changes in kidney and biochemical changes in urine, serum and kidney homogenate. Cystone (500mg/kg, p.o.) was used as reference standard drug. ResultsEthylene glycol–ammonium chloride feeding caused an increase in urinary volume, oxalate, total protein, phosphate and uric acid levels, along with a decrease in urinary excretion of calcium, magnesium and citrate. Supplementation with MBS significantly prevented change in the urinary excretion of calcium, oxalate, phosphate, total protein, uric acid, magnesium and citrate. The MBS supplementation prevented the elevation of serum creatinine, uric acid and blood urea nitrogen levels. The increased calcium, oxalate and phosphate levels in the kidney of lithiatic control rats were significantly reduced by the MBS supplementation. The MBS supplementation caused a significant decrease in the lipid peroxidation of kidney tissue. Histological study revealed minimum damage and less number of calcium oxalate deposits in the kidneys of MBS-treated rats. ConclusionsThese results indicated that the MBS reduced and prevented the growth of urinary stones. However, cystone (500mg/kg) is more effective than the MBS (400mg/kg) in alleviating the urolithiasis. This finding supports the traditional use of B. sensitivum for urolithiasis.

Renal and blood pressure effects from environmental cadmium exposure in Thai children

Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β2-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥1μg/g creatinine. The prevalence of urinary cadmium ≥1μg/g creatinine was significantly higher in girls and in those consuming rice grown in cadmium-contaminated areas. The geometric mean levels of urinary β2-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β2-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children.

Curcumin prevents maleate-induced nephrotoxicity: Relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

English

Diabetic nephropathy is a major sign of kidney dysfunction in diabetes mellitus. The identification of biochemical markers for the clinical course of kidney dysfunction in diabetes mellitus remains a major challenge in the disease management. We investigated the changes in 24 h urine excretion of biochemical indices of type 2 diabetes mellitus. We estimated 24 h urinary excretion of sodium, potassium, bicarbonate, chloride, calcium, inorganic-phosphate, total protein, uric-acid, urea, creatinine, specific gravity, and Ph in 150 type 2 diabetic subjects and their age matched controls by standard methods. Plasma urea and creatinine were also estimated and creatinine and urea clearances calculated for both subjects. The demographic and anthropometric indices of the subjects were obtained from the case files. Results were analyzed statistically by standard statistical spss package version 11.0 to draw conclusion from the data generated. Urinary excretion of total protein, inorganic-phosphate, bicarbonate, urine volume and pH values were significantly higher (p<0.05) in the diabetics than in none diabetic controls, while urinary excretion of calcium, urea, creatinine, uric-acid, urea and creatinine clearances were significantly reduced (p<0.001, p<0.05 respectively) when compared with the controls. Urinary excretion of total protein and fasting glucose have significant direct correlation with the disease duration, while a significant inverse correlation exist between urea, inorganic-phosphate and the disease duration (P<0.05). Significant proteinuria becomes detectable in diabetes mellitus 1-5 years after diagnosis. Urine biochemical indices are altered in type 2 diabetes mellitus and the alterations correlate with the disease duration.