Urine Protein Creatinine Research Articles

Abstract CT006: First-in-class, first-in-human phase 1 trial of VT3989, an inhibitor of yes-associated protein (YAP)/transcriptional enhancer activator domain (TEAD), in patients (pts) with advanced solid tumors enriched for malignant mesothelioma and other tumors with neurofibromatosis 2 (NF2) mutations

Abstract Background: Inactivation of the Hippo pathway is a common finding in MM and other cancers, leading to constitutive YAP activation, but has thus far been undruggable. NF2 encodes Merlin that activates Hippo kinase resulting in inactivation of YAP, which is the major effector of Hippo signaling. NF2-deficient tumors, often due to inactivating NF2 mutations (NF2m), are dependent on YAP for growth. VT3989 is an oral, highly potent and selective inhibitor of TEAD palmitoylation, which blocks YAP function and has shown promising preclinical activity. Materials and Methods: This FIH trial used a 3 + 3 dose escalation design and evaluated VT3989 from 25 to 200 mg QD continuously and 50 to 200 mg intermittently. Pts with refractory solid tumors, ECOG PS 0-1, serum albumin > 2.5, urinary protein creatinine ratio ≤ 0.5 mg/mg and albumin creatinine ratio ≤ 100 mg/g were enrolled. Objectives were to determine the safety, tolerability and recommended Phase 2 dose (RP2D) of VT3989; to evaluate antitumor activity, pharmacokinetics (PK) and correlate NF2m and other alterations in tumor and ctDNA with response. Results: 67 pts have been enrolled. Median age 63.5y (21-83y), ECOG PS 0:1 13:54 pts. Median prior therapies 3 (range 0-8). Tumor types: 42 MM (29 pleural and 13 non-pleural) and 25 solid tumors including 9 meningioma and 4 sarcoma pts. 34 pts had NF2m (29 somatic and 5 germline). All MM pts had progressed on prior platinum/pemetrexed; all but 2 had prior immune checkpoint inhibitors. VT3989 is safe and well tolerated with no dose limiting toxicities. No MTD was defined up to 200 mg QD. The most common AEs are proteinuria, albuminuria and peripheral edema, mainly observed with the continuous schedule. There were 7 possibly related G3 AEs (fatigue, ALT, AST, dehydration, dyspnea, hypotension and peripheral edema) and 1 G4 cardiomyopathy. No pt developed decreased renal function or nephrotic syndrome. VT3989 has a 12-15 day half-life, dose proportional PK and reaches steady state within 2 weeks. Seven pts (6 refractory MM and 1 NF2m sarcoma) achieved RECIST v1.1 partial responses (PRs) with 4 confirmed, 3 unconfirmed (1 pending). 3 PRs in MM pts are ongoing up to 18+ months. The clinical benefit response rate (PR + SD > 8 weeks, per protocol) in MM pts is 57%. Of the 6 MM pts (1 pericardial, 1 pleural/peritoneal and 4 peritoneal) with PR, 2 have NF2m, 3 are wildtype, and 1 is unknown. Conclusions: VT3989 is safe and well tolerated with durable RECIST v1.1 antitumor responses in pts with advanced MM and NF2m cancers, providing the first early clinical proof-of-concept for effectively drugging the Hippo-YAP-TEAD pathway. RP2D optimization including further schedule evaluation and expansion are ongoing in pts with MM and NF2m tumors. Citation Format: Timothy A. Yap, David J. Kwiatkowski, Jayesh Desai, Ibiayi Dagogo-Jack, Michael Millward, Hedy L. Kindler, Anthony W. Tolcher, Sophia Frentzas, Archie W. Thurston, Len Post, F Andrew Dorr. First-in-class, first-in-human phase 1 trial of VT3989, an inhibitor of yes-associated protein (YAP)/transcriptional enhancer activator domain (TEAD), in patients (pts) with advanced solid tumors enriched for malignant mesothelioma and other tumors with neurofibromatosis 2 (NF2) mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT006.

Therapeutic Effect of Triptolide Polymer Mesoscale Nanoparticles on Diabetic Nephropathy Mice

Triptolide (TP) has potential adoption value in the treatment of nephropathy, but its poor water solubility causes toxicity and side effects to various degrees in the kidney, liver, and other organs. In this research, TP-mesoscale nanoparticles (TP-MNPs) were synthesized by the amide reaction of poly(lactic-co-glycolic acid) (PLGA) and methoxy polyethylene glycol amine (mPEG-NH2) as drug carrier materials. The structure of TP-MNPs was characterized by 1H NMR, scanning electron microscopy (SEM), and zeta potential using a nanoparticle potential analyzer. Liquid chromatography–mass spectrometry (HPLC–MS) was utilized to determine the content of TP in TP-MNPs and calculate the entrapment rate (ER) and drug loading (DL) of TP-MNPs. The cytotoxicity of TP-MNPs was detected by CCK8. Eight mice were enrolled in Blank group (no treatment), and the other 24 model group animals were rolled into model group (DM), TP group (TP intervention), and TP-MNP group (TP-MNPs intervention) randomly, with eight mice in each group. The urine protein content, serum albumin (Alb), blood glucose (Glu), creatinine (Cre), total cholesterol (TCHO), and triglyceride (TG) contents of mice in various groups after intervention were compared. The results revealed that average diameter of MNPs was (379.6±26.44) nm, that of TP-MNPs was (424.3±56.29) nm, and average zeta potentials of TP, MNPs, and TP-MNPs were (−28.29±3.85) mV, (−15.51±1.79) mV, and (−13.45±1.81) mV, respectively. The curve changed with TP concentration. With increasing TP concentration, the ER of TP-MNPs decreased drastically, and the DL demonstrated a drastic upward trend. Furthermore, the cell activities of HK-2, NRK-52E, LO2, and AML-12 treated with TP-MNPs were higher versus TP group (P <0.05). Urine protein content, body weight, renal index, serum Glu, TCHO, and TG content in the DM group were markedly superior to Blank group (P <0.001), while urine protein content in TP-MNP group was considerably inferior to the DM group (P <0.01). Alb and Cre in the serum of mice in DM group were substantially lower versus Blank group (P <0.01), while those in TP group were lower than Blank group (P <0.05). Alb and Cre in TP-MNP group were superior to DM group (P <0.05). In summary, TP-MNPs prepared in this research had ideal biocompatibility, could effectively improve urinary protein, body weight, renal index, and serum biochemical indexes caused by DM, and had a certain therapeutic effect on diabetic nephropathy (DN) mice.

Can use of the serum anti-PLA2R antibody negate the need for a renal biopsy in primary membranous nephropathy?

Since the emergence of the anti-PLA2R antibody (PLA2R-Ab) test, nephrology practice has not changed dramatically, with most nephrologists still relying on a kidney biopsy to diagnose membranous nephropathy. In this study, we examined the clinical accuracy of the anti-PLA2R antibody test using ELISA in routine clinical care. We conducted a retrospective analysis of PLA2R-Ab testing in 187 consecutive patients seen at a single UK centre between 2003 and 2020. We compared the kidney biopsy findings with the PLA2R-ab antibody test. Patients' demography, urine protein creatinine ratios, serum albumin, and treatment characteristics including supportive and immunosuppressive treatment were recorded. The clinical accuracy of the test (e.g. sensitivity and specificity, positive [PPV] and negative [NPV] predictive values) was calculated using the kidney biopsy findings as the diagnostic reference. Mean levels of PLA2R-Ab titre in primary membranous nephropathy were 217RU/ml in comparison to 3RU/ml for both secondary membranous nephropathy and other diagnoses. Most patients with a positive PLA2R-Ab test had a confirmed renal biopsy diagnosis of primary membranous nephropathy with: PPV of 97.3%, sensitivity 75.5%, NPV was 79.8% and specificity was 97.8% at a cut-off threshold of >20 RU/ml. The anti-PLA2R antibody test is a highly specific test for diagnosing membranous nephropathy, and the test has the potential to allow for the diagnosis and treatment in up to 75% of PMN cases without the need for a renal biopsy. Nevertheless, patients with negative PLA2R-Ab tests will still require a biopsy to confirm their diagnosis.

KID-T, a unique polyherbal extract, improves feline patients with azotemia and uremia: A pilot study

Cats with azotemia and uremia are increasingly treated with integrative and alternative treatments, including herbal medicines. KID-T (Sin-gi-hwan) is a supplement made of 100% natural herbs and contains 18 herbs, and the components were designed to improve renal function in. Feline renal patients with azotemia and uremia were recruited, and the efficacy of KID-T was examined. Four cats were treated with oral KID-T twice a day for 3 months, and blood biochemical profiles were examined to monitor the toxicity and efficacy of KID-T each month. KID-T was well-tolerated and relatively safe during the treatment period. After 3 months, ammonia, blood urea nitrogen, and creatinine levels were relatively close to the normal reference range in all cats, and the urine protein–creatinine ratio decreased. Biochemical profile and clinical examination exhibited a stabilized status of renal function for 3 months. Overall, KID-T improves and maintains feline renal function, and future studies should evaluate other potential benefits of KID-T in feline renal patients, including correlative assessments of renal function, quality of life improvement, and patient-owner satisfaction.

Progression of chronic kidney disease among black patients attending a tertiary hospital in Johannesburg, South Africa.

Chronic kidney disease (CKD) is a major public health issue worldwide and is an important contributor to the overall non-communicable disease burden. Chronic kidney disease is usually asymptomatic, and insidiously and silently progresses to advanced stages in resource limited settings. A prospective longitudinal study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2022. Demographic and clinical data were extracted from the ongoing continuous clinic records, as well as measurements of vital signs and interviews at baseline and at follow up. Patients provided urine and blood samples for laboratory investigations as standard of care at study entry (0) and at 24 months, and were followed up prospectively for two (2) years. Data were descriptively and inferentially entered into REDcap and analysed using STATA version 17, and multivariable logistic regression analysis was used to identify predictors of CKD progression. A total of 312 patients were enrolled into the study, 297 (95.2%) patients completed the study, 10 (3.2%) patients were lost to follow and 5 (1.6%) patients died during the study period. The prevalence of CKD progression was 49.5%, while that of CKD remission was 33% and CKD regression was 17.5%. For patients with CKD progression the median age at baseline was 58 (46-67) years, the median eGFR was 37 (32-51) mL/min/1.73 m2, median urine protein creatinine ratio (uPCR) was 0.038 (0.016-0.82) g/mmol and the median haemoglobin (Hb) was 13.1 (11.7-14.4) g/dl; 95.2% had hypertension, 40.1% patients had diabetes mellitus and 39.5% had both hypertension and diabetes mellitus. Almost half (48.3%) of patients with CKD progression had severely increased proteinuria and 45.6% had anaemia. Variables associated with higher odds for CKD progression after multivariable logistic regression analysis were severely increased proteinuria (OR 32.3, 95% CI 2.8-368.6, P = 0.005), moderately increased proteinuria (OR 23.3, 95% CI 2.6-230.1, P = 0.007), hypocalcaemia (OR 3.8, 95% CI 1.0-14.8, P = 0.047), hyponatraemia (OR 4.5, 95% CI 0.8-23.6, P = 0.042), anaemia (OR 2.1, 95% CI 1.0-4.3, P = 0.048), diabetes mellitus (OR 1.8, 95% CI 0.9-3.6, P = 0.047), elevated HbA1c (OR 1.8, 95% CI 1.2-2.8, P = 0.007) and current smoking (OR 2.8, 95% CI 0.9-8.6, P = 0.049). Our study identified a higher prevalence of CKD progression in a prospective longitudinal study of black patients with CKD compared with literature reports. CKD Progression was associated with proteinuria, diabetes mellitus, elevated HbA1c, anaemia, hypocalcaemia, hyponatraemia and current smoking in a cohort of black patients with CKD who had controlled hypertension and diabetes mellitus at baseline.

Study on correlation of urine specific gravity with other laboratory parameters of urine in children with Nephrotic syndrome

Nephrotic syndrome is a frequent childhood kidney disease in which proteinuria is a significant characteristic. Proteinuria can be a benign condition as well as indicates severe underlying renal or systemic diseases. The variation in the prevalence of proteinuria may occur based on the definition used or the evaluation time of the test. Proteinuria is present in up to 10% of routine urine testing in school-aged children, although this decreases to 0.1% with repeated testing. The study aimed to analyze the correlation of urinary specific gravity with other laboratory parameters of urine in children with nephrotic syndrome. Methods: This cross-sectional study was conducted in the Department of Pediatric Nephrology (NIKDU), Dhaka from October 2019 to June 2021, and a total of 153 patients with nephrotic syndrome were enrolled after taking written consent. Urine samples were collected for both 24 hours and spot for estimation of urinary protein, urinary creatinine, dipstick protein, and specific gravity by dipstick method. Spot urinary Protein Creatinine Ratio (PCR) and 24 hours urinary protein were also estimated. Results: Among 153 study subjects maximum (44.4%) were 2-5 years old followed by 58 (37.9%) who were 5-10 years and 27 (17.6%) were >10 years old. Boys (61.4%) were more predominant than girls (38.6%). Mean 24 hours urinary volume was 1097.78±662.63 ml, 24 hours urinary creatinine was 32.17±23.70 mg/dl, 24 hours urinary total protein was 851.42±123.68 mg/dl, 24 hours urinary total protein (UTP) was 7.52±7.65 gm/m2/24 hours urinary specific gravity 1.020±0.02, spot urinary protein 989.49±1136.73 mg/dl, spot urinary creatinine was46.09±43.73 mg/dl, spot urinary PCR was 21.87±18.24 mg/mg and spot urinary specific gravity was 1.020±0.01. The Scatter diagram showed a significant positive correlation of 24 hours urinary specific gravity with 24 hours urinary protein (r=0.169, p=0.037). There was a significant positive correlation of 24 hours specific gravity with 24 hours urinary creatinine (r=0.380, p=<0.001). There was a significant positive correlation of spot urinary protein with spot urinary specific gravity as well (r=0.206, p=0.011). Spot urinary specific gravity showed a significant positive correlation with spot urinary creatinine (r=0.355, p=<0.001). There was a significant negative correlation of spot urinary specific gravity with spot urinary PCR (r= -305, p=<0.001). Conclusion: It can be concluded that urinary specific gravity had a substantial correlation with other laboratory parameters of urine and can be used as an important diagnostic tool for diagnosing proteinuria in children with nephrotic syndrome

Comment on “Cutaneous adverse reactions of COVID‐19 vaccines: A systematic review”

We read with interest the article published by Shafie'ei et al.1 regarding a systematic review and meta-analysis of all reported cutaneous side effects of COVID-19 vaccines. Our experience with COVID-19 cutaneous reactions is largely consistent with prior reports of mild, self-limiting cutaneous reactions.2-4 We note reports describing cutaneous vasculitis following COVID-19 vaccination.5 In contrast to the reported mild cutaneous reactions following COVID-19 vaccination, we report the case of a severe prolonged IgA vasculitis following the single dose Janssen COVID-19 vaccine—Ad.26.COV2.S. A 60-year-old Caucasian woman self-presented to the emergency department due to an extensive painful rash affecting her bilateral lower limbs. She described a petechial rash affecting her lower limbs 8 h post the single dose COVID-19 vaccine 11 days prior. Within 10 days, she had developed extensive palpable purpura circumferentially at both lower limbs from the knee distally as well as affecting her thighs and lower abdomen and was referred to dermatology by the emergency physicians (Figure 1A). This was on a background of psoriasis, psoriatic arthritis and hypertension. Her longstanding medications included naproxen, amlodipine, and fexofenadine, and she denied any symptoms of infection. She was apyrexial, and her systems review and examination were unremarkable. Blood tests taken revealed a mildly elevated c-reactive protein of 14 mg/L (normal: <7 mg/L) and erythrocyte sedimentation rate of 26 mm within the first hour (normal: <13 mm) and a normal white blood cell count of 6.41 × 109/L (normal: 3.5–10.5 × 109/L). A chest x-ray and midstream urine showed no evidence of infection. At this time, super-potent topical steroids were prescribed. A punch biopsy taken from her right lower limb demonstrated findings consistent with a leukocytoclastic vasculitis (Figure 2). Direct immunofluorescence demonstrated IgA deposits within vasculature. On follow-up review, tense bullae were seen at her bilateral ankles. Treatment prescribed at this time consisted of tapering oral steroids, oral antibiotics for secondary infection and wound care. The bullae ruptured to leave multiple punched-out and exquisitely painful ulcers (Figure 1B). It was noted that her urinary protein creatinine (UPCR) ratio was uptrending and rose to a value in excess of 100 mg/mmol (normal 0–15 mg/mmol). Complete resolution of the aforementioned lower limb ulceration was noted following 5 months of oral steroid treatment (Figure 1C). Imaging, colonoscopy, and mammography were negative for malignancy. IgA vasculitis represents a small vessel vasculitis brought about by the activation of neutrophils and deposition of IgA at perivascular sites.6 We note a prior case report of postvaccination IgA vasculitis resolving 4 weeks after onset.5 In our case, the complete resolution of the vasculitis and secondary ulceration were noted following 5 months of treatment with oral corticosteroids, which represents the longest reported case. Additionally, our patient had secondary renal involvement with preserved renal function. Her regular medications of naproxen and amlodipine were commenced 5 years prior to this presentation and so were deemed unlikely to be causative. Malignancy and infection were out-ruled. While this presentation may have been coincidental, the relationship between immune complex vasculitis and vaccination has been reported5 and represents the most likely pathophysiological explanation in our patient's case. We feel this case is worth highlighting as it demonstrates a prolonged and severe cutaneous reaction to COVID-19 vaccination. All authors contributed to the editing and execution of this piece. None. The authors report no conflict of interest. The data that support the findings of this study are openly available in Pubmed at https://pubmed.ncbi.nlm.nih.gov/. The patient reported in this article has provided written consent for clinical images to be used in publication.

Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome

BackgroundGlomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians.MethodsAdriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro.ResultsThe contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway.ConclusionICA enhances the therapeutic effect of DEX on the nephrotic syndrome.

The first study on urinary loss of iron and transferrin in association with proteinuria in dogs with chronic kidney disease.

Anemia is an important factor in surviving chronic kidney disease (CKD). Anemia in CKD is associated with various factors, such as inadequate production of erythropoietin and the availability of iron and its binding protein. Reduced total iron-binding capacity (TIBC) and iron concentrations may be related to their urinary loss along with proteinuria. This study aimed to determine the urinary loss of iron and transferrin (TF) in relation to the degree of proteinuria. The study was performed on 37 dogs with CKD. Dogs were divided according to the severity of proteinuria into two groups based on the mean of urinary protein-creatinine (UPC) ratio into UPC ratio <4 and UPC ratio >4. The hematocrit (HCT), blood chemistries, plasma iron, plasma TF, UPC ratio, urinary iron per creatinine ratio (U-Iron/CR), and urinary TF per creatinine ratio (U-TF/CR) were evaluated. Anemia was associated with the severity of renal impairment as demonstrated by reduction of HCT when staging of CKD was higher. Dogs with UPC ratio >4 had higher urinary loss of both U-Iron/CR (p < 0.01) and U-TF/CR (p < 0.001) with lower plasma TIBC (p < 0.001). The UPC ratio was positively correlated with both U-Iron/CR (r = 0.710, p < 0.001) and U-TF/CR (r = 0.730, p < 0.001) but negatively with TIBC (r = -0.462, p < 0.01). Proteinuria was associated with urinary loss of both iron and TF which may contribute to anemia in CKD.

Aspirin alleviates the symptoms of immunoglobulin A nephropathy via suppressing platelets-mediated non-canonical NF-κB activation in B cells

Purpose: Antiplatelet aggregation drugs, such as aspirin, can alleviate pathological renal damage in immunoglobulin A (IgA) nephropathy, although the precise mechanism is unclear.&#x0D; Methods: The serum levels of platelet factor 4 (PF4), IgA, and platelet-activating factor (PAF) were assessed by enzyme-linked immunosorbent assay in IgA nephropathy patients and TANK-binding kinase 1 (TBK1)-/- tumor necrosis factor (TNF)-/- mice. The deposition of IgA in glomeruli was detected by immunofluorescence. Phorbol-12-myristate-13-acetate (PMA) induced platelets activation was examined by the cell counting kit 8 assay. B cells were further stimulated with lipopolysaccharides (LPS) or plus platelets supernatant, or combined with nuclear factor kappa-B (NF-κB) inducing kinase (NIK) inhibitor, NIK SMI1.&#x0D; Results: Increased serum IgA and proportion of activated platelets were observed in IgA nephropathy patients. TBK1-/-TNF-/- mice had significant increased urinary protein and serum creatinine, and IgA deposition in glomeruli. Up-regulated serum PF4 and PAF were observed in both the IgA nephropathy patients and TBK1-/-TNF-/- mice. Aspirin suppressed the deposition of IgA in glomeruli of TBK1-/-TNF-/- mice with down-regulated platelets activation. Platelets supernatant could promote the proliferation of B cells with up-regulated IgA and sCD40L secretion and up-regulated P52 and RelB expression, which could be inhibited by NIK SMI1 administration.&#x0D; Conclusion: TBK1-/-TNF-/- mice demonstrate IgA nephropathy phenotype, which could be alleviated by aspirin administration via inhibiting platelets induced non-canonical NF-κB activation mediated IgA production in B cells.

Bartonella henselae Infective Endocarditis: A Rare Cause of Pauci-Immune Necrotizing Glomerulonephritis—A Case Report

Bartonella sp. are the most common causes of culture-negative infective endocarditis (IE) cases in the United States. Although, infection-related glomerulonephritis can frequently mimic primary vasculitis due to pauci-immune pattern, majority of previously reported cases of Bartonella henselae-associated glomerulonephritis have immune-complex deposits on immunofluorescence. We present a rare case of B henselae IE-related pauci-immune necrotizing glomerulonephritis. Timely recognition of this atypical presentation led to appropriately directed medical therapy. A 33-year-old Caucasian male with a history of human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART), alcohol abuse, previous subarachnoid hemorrhage (SAH), and recent wisdom tooth extraction (on amoxicillin) was transferred from an outside hospital for further evaluation of severe headache. He was diagnosed with an SAH and right anterior cerebral artery mycotic aneurysm. The serum creatinine at the outside hospital was 292 umol/L (3.3 mg/dL) with a previously normal baseline around 2 years ago. The serum creatinine at our institution was 256 umol/L (3.0 mg/dL). The urinalysis demonstrated +100 protein, +3 blood and 29 red blood cells/high power field. The urine protein creatinine ratio (UPC) was 1.7 g/g. Serologic evaluation was positive for a low C4 10.2 mg/dL, elevated rheumatoid factor 40 IU/mL and an elevated proteinase 3 (PR-3) antineutrophilic cytoplasmic antibodies (ANCA Ab) 4.0 U/mL. A transesophageal echocardiogram (TEE) showed echo densities on both mitral and aortic valve. Blood cultures were negative. Further serologic evaluation was positive for B henselae IgG titer of 1:2560 (normal <1:320) with a negative IgM titer. A percutaneous kidney biopsy revealed pauci-immune necrotizing glomerulonephritis, with 14/16 glomeruli globally sclerotic, and 2 glomeruli with active segmental necrotizing lesions. There was no evidence of immune-complex deposition on immunofluorescence or electron microscopy. Clinical findings were consistent with B henselae IE associated mycotic aneurysm and necrotizing glomerulonephritis. Empiric treatment for an active glomerulonephritis with immunosuppressive agents was deferred on admission, given concern for an underlying infectious process and mycotic aneurysms in an HIV-positive patient. He received antibiotic treatment with doxycycline and ceftriaxone with gentamicin for synergy. Despite this, the mitral and aortic valve regurgitation worsened, and he developed congestive heart failure requiring aortic valve replacement and mitral valve repair. The explanted aortic valve was positive for B henselae by polymerase chain reaction (PCR) confirming the diagnosis of B henselae IE. Immunosuppression was deferred due to timely identification of an atypical presentation of B henselae-associated ANCA antibodies-positive, pauci-immune necrotizing glomerulonephritis. A course of antibiotic treatment resulted in improved renal functions along with undetectable B henselae and PR3 Ab titers. The serum creatinine decreased to 176 umol/L (2 mg/dL) and remained stable 12 months after discharge. B henselae IE should be suspected in patients with pauci-immune necrotizing glomerulonephritis and culture-negative IE. This is imperative for optimal decision making in the management of such patients. Having high clinical suspicion can avoid unnecessary and potentially deleterious use of immunosuppressive agents.

Effect of deferasirox on renal function in thalassemic children

Abstract Background: Iron-chelating therapy causes improvement in the life expectancy of thalassemic patients. Deferasirox (DFX) is an oral iron chelator with an established dose-dependent efficacy, though alteration of renal function has been observed in many studies. In the present study, we evaluated the effect of treatment with DFX on renal function. Materials and Methods: This quasi-experimental study was done in the Thalassemia Center of Bangladesh Shishu Hospital and Institute from June 2019 to July 2021, where 50 thalassemia major and E-β thalassemia children aged 2–18 years old were included. Blood urea nitrogen (BUN), serum creatinine, spot urinary protein creatinine ratio, spot urinary calcium creatinine ratio, and estimated glomerular filtration rate (eGFR) were measured. If renal functions were normal, DFX was started at a dose of 25 mg/kg/day. After 6 months of DFX treatment, the abovementioned investigations were repeated and analysis was done. The study variables were analyzed by paired t-test. P value &lt;0.05 was considered significant. Results: The mean age of the thalassemic children was 5.21 ± 1.72 years. Before treatment, mean serum creatinine was 39.78 ± 3.12 μmol/L, and after 6 months, serum creatinine was increased but not statistically significant. The mean value was 40.50 ± 3.39 μmol/L after 6 months (P value 0.071). There was no significant change of BUN. Initially, the mean BUN was 3.39 ± 0.76 mmol/L, and 6 months after treatment, it was 3.45 ± 0.70 mmol/L. Initially, the spot urinary protein creatinine ratio was 0.12 ± 0.04, and after 6 months, the mean value was 0.43 ± 0.24. it was significantly increased (P value &lt;0.001). Initially, the spot urinary calcium creatinine ratio was 0.068 ± 0.043, and after treatment, it was significantly raised. The mean value was 0.191 ± 0.168 (P value &lt;0.001). After 6 months of treatment with DFX, 35 patients developed mild proteinuria, and eight patients developed hypercalciuria. There was no significant change of eGFR before and after treatment. Conclusions: In this study, we got significant proteinuria and hypercalciuria but nonsignificant changes in serum creatinine, BUN, and eGFR.

Assessment of Correlation of Serum Lipid Profile and Urinary Protein Creatinine Ratio with Occurrence of Gestational Hypertension in Pregnant Mothers in a Tertiary Care Hospital, Kolkata

After 18 months study from 1st April, 2021 to 30th September, 2022 on the pregnant mothers in a tertiary care hospital, i.e., in R.G. Kar Medical College &amp; Hospital, Kolkata, we have observed that there is significant rise of Urinary Protein Creatinine ratio in spot urine sample of Gestational hypertensive women in comparison to normotensive pregnant women. We may opine that, measurement of Spot Urinary Protein Creatinine Ratio as well as Serum Triglyceride, Total Cholesterol, different components of Cholesterol and calculation of their ratios may be used as precautionary steps, to take the necessary actions to prevent the complications of Gestational hypertension, i.e., graver grades of Pregnancy Induced Hypertension (PIH), namely, Preeclampsia and Eclampsia.

Intervention Mechanism of Niao Du Kang Mixture on the EMT Process of Peritoneal Fibrosis Based on the Wnt/β-Catenin Signaling Pathway.

Quantification of 24-hour urine protein (24 h-Upro) and serum creatinine (Scr) levels was performed. The protein and mRNA expression levels of E-cadherin, α-SMA, collagen I, β-catenin, Wnt-1, and LEF-1 in peritoneal tissue were measured. In addition, the pathological morphology and ultrastructure of peritoneum were observed. After 5/6 nephrectomy + high glucose peritoneal dialysate + lipopolysaccharide (LPS) treatment, the Scr and 24 h-Upro of rats increased compared with normal rats, and the peritoneal tissue was damaged and thickened, showing fibrotic changes. Compared with the model group, the Scr and 24 h-Upro levels and the levels of E-cadherin, α-SMA, Wnt-1, collagen I, and LEF-1 protein expression in each Niao Du Kang mixture dosage group decreased. The protein expression of β-catenin and the mRNA expression of E-cadherin, α-SMA, Wnt-1, collagen I, β-catenin, and LEF-1 decreased in the high and medium Niao Du Kang mixture dose groups. Hematoxylin and eosin staining showed that the peritoneum of the rats was not only thicker in the model group than in the sham operation group (P < 0.01) but also accompanied by apparent inflammatory cell infiltration, tissue edema, and fibrosis. Compared with the model group, all the Niao Du Kang mixture groups demonstrated various degrees of mitigation in peritoneal thickness and fibrosis (P < 0.01). The strongest effect was observed in the medium-dose group. Transmission electron microscopy showed that the degree of injury of the peritoneal mesothelial cells was ranked as follows: model group > positive drug group > Niao Du Kang mixture high-dose group. The Niao Du Kang mixture may effectively decrease the peritoneal thickness and fibrosis degree through its effect on the Wnt/β-catenin signaling pathway involved in EMT. The present study provides data that assist in elucidating the potential function of the Niao Du Kang mixture in treating or preventing PF.

Studies on the metabolism and mechanism of acteoside in treating chronic glomerulonephritis

Ethnopharmacological relevanceActeoside (ACT) is the main ingredient derived from the leaves of Rehmannia glutinosa (Dihuangye). Dihuangye has the function of clearing heat, replenishing qi and activating blood, nourishing yin and tonifying kidney in traditional Chinese medicine. Recent studies have demonstrated that Dihuangye can be used to treat nephritis and ACT is a promising antinephritic agent. Aim of the studyTo clarify the metabolites of ACT in biological samples and investigate the renoprotective effect and mechanism of ACT in rats with chronic glomerulonephritis (CGN). Materials and methodsIn this study, the biotransformation of ACT in rat biological samples was clarified by quadrupole time-of-flight tandem mass spectrometry. The metabolites were validated by urine samples in nephropathy model rats. The effect of ACT and its metabolites was evaluated by glomerular podocyte injury due to high glucose. Based on an analysis of the ingredients in vivo, the potential therapeutic targets in the treatment of CGN were investigated by using network pharmacological analysis and molecular docking. Then, the renoprotective effect and mechanism of ACT were determined in rats in a passive Heymann nephritis (PHN) model. ResultsA total of 49 metabolites of ACT were detected and identified. Meanwhile, 21 metabolites were detected in nephropathy model rats. ACT was absorbed rapidly and transferred from the kidney, and the metabolites were eliminated via urine. The whole process lasted approximately 8 h. ACT had a significant protective effect on glomerular podocytes damaged by high glucose and 3,4-dihydroxyphenylacetic acid might be the main metabolite of ACT underlying its functions in vivo. The network pharmacology and molecular docking results showed 84 ACT-CGN targets, among which MAPK1, HRAS, AKT1, EGFR, and others were a highly correlated. In the PHN rat model, ACT significantly reduced the 24-h urine protein and serum creatinine concentrations, suppressed the leukocyte CD18 expression levels, decreased the serum tumor necrosis factor α (TNF-α) levels and tended to reduce serum interleukin 6 (IL-6) levels. ACT significantly reduced the platelet aggregation rate and inhibited the proliferative activity of splenic lymphocytes in response to the mitogen concanavalin A. Meanwhile, ACT inhibited transforming growth factor-β and fibronectin expression in renal tissues and dose-dependently inhibited TNF-α and IL-6 production in RAW264.7 mouse macrophages at doses ranging from 1.8 to 1330 μg/mL. ConclusionsACT had therapeutic effects on PHN rats, and its mechanism might be related to the inhibition of intercellular or intercellular-matrix adhesion, suppression of inflammatory response, regulation of immune function, improvement of tissue hemodynamics and hemorheology, and relief of fibrotic lesions.

Serum level of hepcidin in chronic kidney disease - A hospital-based study from South India

Background: The term “chronic kidney disease (CKD)” refers to a variety of pathophysiologic conditions characterized by impaired kidney function and a steady fall in glomerular filtration rate. CKD is a slowly progressive silent epidemic that affects approximately 12% of the world population. Aims and Objectives: The aim of the study was to estimate the level of serum Hepcidin in patients with CKD compared to healthy controls. Materials and Methods: Hundred subjects both male and female over the age of 18 were included in the study and informed consent was obtained from each of them. The study population was divided equally into two groups. Blood serum was collected to estimate level of hepcidin, urea, creatinine, ferritin, iron, total iron binding capacity, hs C-reactive protein (CRP), and total proteins. Urine was collected in a sterile container for urine protein creatinine ratio. Results: Hepcidin could be a prognostic marker in the clinical outcome of CKD especially in the progression of CKD. There was a highly significant positive correlation of serum Hepcidin with hsCRP, ferritin, creatinine, urea, urine protein creatinine ratio, and erythrocyte sedimentation rate. Significant negative correlation of serum Hepcidin with Creatinine Clearance, Iron, TIBC, Transferrin saturation, Hemoglobin, and Total Proteins had been observed. Conclusion: The current study showed that patients with CKD and anemia have considerably higher serum hepcidin concentrations. The level of hepcidin increases as disease progresses in CKD patients. Hepcidin, mediator of anemia in CKD is the potential target to treat anemia in them to prevent death due to cardiovascular complications and improve their quality of life.

Rituximab in patients with membranous nephropathy and kidney insufficiency.

Introduction: Patients with membranous nephropathy and kidney insufficiency have an extremely high risk of progression to end-stage renal disease. Whether rituximab can effectively treat membranous nephropathy patients with renal dysfunction remains unknown at present. The aim of our study was to evaluate the effectiveness and safety of rituximab (RTX) in membranous nephropathy with kidney insufficiency. Methods: We retrospectively analyzed the clinical data of 35 membranous nephropathy patients with kidney insufficiency administered in the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2021. Patients were followed every 1–3 months for a total of 6 months. Clinical data were collected including anti-phospholipase A2 receptor antibody (anti-PLA2R antibody) quantification, 24-h urinary protein, serum albumin, and serum creatinine. The percentage of patients who achieved clinical remission was measured. Results: There were 7 (20%) patients who achieved complete or partial response at 6 months after RTX treatment. After 6 months of treatment, patients were clinically improved as evidenced by significant improvements in anti- PLA2R antibody titer [7.70 (5.72, 16.72) vs. 59.20 (17.70, 187.50) RU/ml, p < 0.001], 24-h urine protein [7.04 (4.43, 8.90) vs. 10.15 (4.83, 13.57) g/d, p < 0.001], serum albumin [30.55 (24.97, 33.27) vs. 21.40 (16.75, 25.00)g/L, p < 0.001], serum creatinine [99.50 (75.25, 140.25) vs. 152.00 (134.50, 232.50) µmol/L, p = 0.022], and estimated glomerular filtration rate (eGFR) [78.29 (50.15, 101.55) vs. 41.12 (26.53, 51.41) ml/min/1.73 m2, p = 0.045]. There were no significantly differences between responders and nonresponders in the baseline levels of anti-PLA2R antibodies, proteinuria, serum albumin, and renal function. After the RTX treatment, anti-PLA2R antibodies turned negative in all responders, but the antibody level persisted maintained positive in all but 5 nonresponders. The patients who achieved response maintained a stable kidney function during the study period, with eGFR 29.03 (28.76, 35.07) ml/min/1.73 m2 before rituximab treatment and 62.73 (62.34, 63.13) ml/min/1.73 m2 at the end of follow-up (p = 0.053). Conclusion: RTX therapy might be an alternative treatment in reducing proteinuria and maintaining stable renal function among membranous nephropathy patients even with kidney insufficiency.

Histopathologic and clinical features of diabetic nephropathy alone and with concomitant nondiabetic renal diseases

Background and objective: Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM) and one of the leading causes of end-stage kidney disease. The aim of the present study was to evaluate the histomorphological and clinical profiles of DN and associated non-diabetic renal dieases (NDRD) in diabetic patients. Materials and methods: The study was carried out at the Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Dhaka, from July 2019 to December 2020. Renal biopsy samples from known diabetic patients were included in the study. The formalin-fixed tissues were stained with haematoxylene &amp; eosin (H&amp;E), Periodic acid Schiff (PAS), Masson Trichrome (MT) and Jones Methanamine Silver (JMS) stains. Tissues were stained for IgG, IgA, IgM, C3, C1q, kappa and lambda for direct immunofluorescence (DIF) study. DN was histologically classified according to Tervaert classification system. Interstitial fibrosis and tubular atrophy (IFTA) as well as arteriolar hyalinization scoring was also done. Clinical information was retrieved from the patient’s information sheet. Results: Total 46 biopsy samples from DN cases were included in the study. The mean age of the cases was 46.76+10.63 years, including 36 males and 10 females. The most common clinical presentation was nephritic range proteinuria (n=32, 69.56%). Among all, 27 (58.69%) patients had haematuria. The mean serum creatinine level was 4.28+2.61 mg/dl, and 80.43% had serum creatinine levels &gt;1.5 mg/dl. Histopathologic examinatiom revealed type III DN in 26 (56.5%) and type IV DN in 11 (23.9%) cases. IFTA score 1 (&lt;25%) was seen in 20 (43.5%), score 2 (25-50%) in 19 (41.3%) and score 3 (&gt;50%) in 7 (15.2%). Vascular hyalinization score-2 in 25 (54.3%), score-1 in 14 (30.4%) and score-0 in 7 (15.2%). DN class II, III and IV were associated with high urinary total protein (UTP) and serum creatinine levels. Among the histologic changes, percentage of glomerular sclerosis, the mean IFTA score and vascular hyalinization score were found to be highest in class IV DN, and all were significantly associated with histologic glomerular DN classes (p= &lt;0.05). Of the total cases, 21 (45.65%) were found with nondiabetic renal diseases (NDRD), the most common feature was focal segmental glomerulosclerosis (FSGS) (26.57%), followed by IgA nephropathy and post-infectious glomerulonephritis (PIGN). Among 46 cases, one post-transplant biopsy was included, which revealed class II DN along with features of calcineurin inhibitor toxicity. Conclusion: Tervaert’s histologic classification of our cases revealed class III DN lesions as the predominant one, and the classes had a significant association with age of the patient, serum creatinine level, mean IFTA, arteriolar hyalinization and NDRD. Among the NDRD, FSGS was the most common pathology. IMC J Med Sci. 2023; 17(1): 003. DOI: https://doi.org/10.55010/imcjms.17.003 *Correspondence: Sk Md Jaynul Islam, Department of Histopathology, Armed Forces Institute of Pathology, Dhaka Cantonment, Dhaka, Bangladesh. Email: jaynul.islam@gmail.com

Urine creatinine concentration influences the prognostic value of proteinuria for MACE prediction from the findings of the KNOW-CKD study

Proteinuria is typically quantified according to the spot urine protein–creatinine ratio (UPCR) and an association with cardiovascular events has not been thoroughly investigated in chronic kidney disease (CKD) patients. We investigated whether the severity of proteinuria assessed by spot UPCR is associated with an increased risk for cardiovascular outcomes in the CKD population, and whether the relationship is influenced by urine creatinine concentration. We analyzed 1746 patients enrolled as part of The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable Cox proportional hazard analysis was performed to evaluate models with proteinuria as a predictor of renal events and extended major adverse cardiovascular events (eMACEs). Risk for renal events was significantly associated with proteinuria across all eGFR and UPCR categories. By contrast, risk for eMACEs increased significantly with UPCR in patients with eGFR ≥ 60 mL/min/1.73 m2 (hazard ratio [HR] 2.109; 95% confidence interval [CI] 1.375–3.235; P = 0.001), but not in patients with eGFR < 60 mL/min/1.73 m2 (HR 1.086; 95% CI 0.910–1.296; P = 0.358). However, in those with the lower eGFR, risk for eMACEs increased significantly with UPCR in participants with urine creatinine concentration ≥ 95 mg/dL (HR 1.503; 95% CI 1.047–2.159; P = 0.027). In non-dialysis CKD patients, the prognostic value of UPCR for eMACEs is weakened in patients with reduced eGFR levels, for whom it has prognostic significance only in patients with high urine creatinine concentration.

Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy