Nephrotoxicity induced by vascular endothelial growth factor inhibitors

Vascular endothelial growth factor (VEGF) is a special mitogen for vascular endothelial cells, an essential endogenous angiogenic cytokine, and the principal controller of vascular growth that plays a fundamental role in therapeutic angiogenesis pathways. VEGF-targeted therapy is categorized into the group of angiogenesis inhibitors that inhibit the expression or the activity of VEGF. It comprises counteracting VEGF antibodies, VEGF receptors, VEGF-trap, and tyrosine kinase inhibitor (TKIs) with selectivity for VEGF receptors. The kidney is both a target and a source of VEGF. VEGF may be a vital mediator to restore some types of renal diseases (e.g., non-diabetic renal diseases) and harmful in some other diseases (e.g., diabetes and diabetes complications). Due to their ability to prevent angiogenesis, VEGF inhibitors have been found as a powerful tool to treat angiogenesis-dependent diseases, including cancer and diabetic retinopathy. VEGF preserves the renal structure and function in normal physiologic conditions. Therefore, all treatments that inhibit the VEGF pathway may lead to renal disorders, especially renovascular diseases such as hypertension, proteinuria, nephrotic syndrome, decreased glomerular filtration rate (GFR), and thrombotic microangiopathy (TMA). In the present study, we reviewed some related reports and associated mechanisms, especially for hypertension and proteinuria.

Glucose transporters in kidney; the role of gender and diabetes mellitus

Sex hormones affect the developmental process and play important roles in the kidney’s structure and functions. Clinical and experimental results have indicated that kidney functions are different between the genders, and they may be associated with the sex hormones, which regulate the expression and action of transporters in the nephron. In the current short review, the data banks including PubMed, Google Scholar, and Scopus were reviewed to achieve the published related articles regarding the role of gender and diabetes mellitus in glucose transport in renal system.

Prevalence of nephropathy and proximal tubule disorder in human immunodeficiency virus patients under tenofovir therapy

Introduction: Tenofovir is a common therapy in human immunodeficiency virus (HIV) patients. Objective: This study was carried out to determine the prevalence of nephropathy and proximal tubule disorder in HIV patients under tenofovir therapy. Patients and Methods: In this study, 160 HIV patients under tenofovir therapy were enrolled and the prevalence of nephropathy and proximal tubule disorder was determined and compared. Results: We found, the proximal tubule involvement in 25%, 6.8%, 2.2% and 0% in first year, 2–5 years , 6–10 years and 11–18 years of disease involvement respectively, (P = 0.02). The mean glomerular filtration rate (GFR) diminution was 2.15%, 10.53%, 12.6% and 17.79%, in the first, 2–5, 6–10, and 11–18 years, respectively, again showing a significant difference between years (P = 0.02). Proteinuria was seen in 13.1% of patients. Conclusion: We concluded that GFR diminution and proximal tubule involvement are common and important to be managed in HIV-positive patients under tenofovir therapy, and discontinuation of drug has no positive effect on GFR.

Kidney complications following COVID-19 vaccination; a review of the literature

Objective: To review the reported cases of kidney injury following vaccination for coronavirus disease 2019 (COVID-19) with a focus on renal pathology. Methods: We searched for case reports of kidney complications after COVID-19 vaccine in PubMed. Results: A total of 36 articles including 49 case reports were reported. These included minimal change disease (n=17), IgA nephropathy (IgAN) (n=15), IgA nephritis/vasculitis (n=5), ANCA glomerulonephritis/vasculitis (n=5), anti-glomerular basement membrane (GBM) nephritis (n=2), and 1 case of each granulomatous vasculitis, acute tubulointerstitial nephritis, scleroderma renal crisis, IgG4-related disease nephritis, and primary membranous nephropathy (MN). Conclusion: We give an overview of the reported cases of post-COVID-19 renal complications. Further investigations of the underlying pathogenesis of post-COVID-19 vaccination renal adverse events are required, as prompt workup, diagnosis, and treatment of patients with renal complications may lead to complete remission, prevent kidney failure, and long-term complications such as end-stage renal disease (ESRD). However, these complications are overall extremely rare and the benefit of vaccination outweighs the potential risks.

A comparative study on the effect of calcitriol and cinacalcet on hyperparathyroidism in hemodialysis patients; a double-blinded randomized clinical trial

Introduction:Chronic kidney disease (CKD) has lots of complication like calcium and phosphate metabolism disorders, hyperparathyroidism, vitamin D deficiency and metabolic acidosis. Objectives: The aim of this study was to determine and compare the effect of calcitriol and cinacalcet on hyperparathyroidism in hemodialysis patients due to end-stage renal disease (ESRD). Patients and Methods: This study was a double-blinded randomized clinical trial, which was conducted on 60 hemodialysis patients in 2017-2018. The patients were randomly assigned to two groups of 30 patients, which one group was treated with cinacalcet and the other group was treated with calcitriol. During this study, phosphorus, calcium and iPTH were measured. Results: The results showed that in the group treated with cinacalcet, the amount of calcium [t(22)=0.294, P>0.05] and the amount of phosphorus [t(22)=1.87, P>0.05] did not change significantly while iPTH values before and after the study had statistically significant difference [t(22)=4.37, P<0.05]. In group treated with calcitriol, the calcium, phosphorus and iPTH values did not change significantly (P>0.05). Calcium changes in the cinacalcet group compared to the calcitriol group [t (47) =-1.14, P>0.05] and also, the amount of phosphorus changes [t (47) =-1.022, P>0.05] was not statistically significant. The iPTH changes were not statistically significant between the two groups however iPTH in the calcitriol group was higher than the cinacalcet group [t (47) =-1.13, P>0.05]. Conclusion: In contrast to calcitriol, cinacalcet significantly reduced iPTH and did not significantly change calcium and phosphorus levels. Trial Registration: The trial was registered by Iranian Registry of Clinical Trials (IRCT) (identifier: IRCT20190702044076N1; https://en.irct.ir/trial/40547, Ethical code# IR.SKUMS.REC.1397.026).

Evaluation of medical treatment in Iranian children with nephrolithiasis

Introduction: Nephrolithiasis has been increasingly recognized in recent years. Urine metabolic abnormality is the main cause of renal stone in children. Therefore, identification and medical treatment of metabolic abnormalities have been suggested as an alternative approach to surgical treatments. Objectives: This study was performed to evaluate the therapeutic effect of urine alkalinization and metabolic management in children with renal stone. Patients and Methods: A total of 300 children (from 408 renal clinics) with nephrolithiasis were enrolled in this study. All of them were treated by supportive managements, including urine alkalinization and specific medical treatment of underlying metabolic abnormality. Improvement was defined as stone resolution, stone passage or decrease of stone dimension. Results: Mean age at diagnosis was 28.7 ± 2.6 months (1-150 months). About 78.8% of patients had metabolic abnormality, of which, hypercalciuria (51.7%) and hypocitraturia (33.4%) were the most common causes, respectively. Resolution of renal stone occurred in 89.7% of patients after one year follow up, more in children less than 5 years (P=0.003), and stones smaller than 5 mm (P<0.001). However, 87.5% of large stones (5-12 mm) improved by medical treatment. Conclusion: Pharmacologic treatment is recommended in young children with small nephrolithiasis. Pharmacologic treatment also suggested as a primary intervention in children with uncomplicated large renal stones, and prior to invasive surgical management.

Examination the antioxidant potentials and antidiabetic properties of phenolic extracts of some Iranian honeys

Introduction: In most ancient cultures, honey has been used for both nutritional and medical purposes. Objectives: In this research, phenolic extracts of four Iranian honeys were evaluated to determine the antioxidant potentials using DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging, nitric oxide (NO) radical scavenging and reducing power by ferric reducing activity of plasma (FRAP) method. Additionally, anti-diabetic properties of honey and phenolic extracts were evaluated by determination of α-amylase and α-glucosidase inhibition. Patients and Methods: Besides, reducing potential was evaluated by ferric-reducing antioxidant power method. Moreover, determination of phenolic and flavonoid contents was performed. Moreover, inhibition of α-amylase and α-glucosidase of honey and phenolic extracts were evaluated. Results: With considering to antioxidant potentials, Gavan (Astragalus) sample showed the greatest phenolic (3817±1.52 mg GAE/100 g), flavonoid contents (3.1±0.005 mg QE/100 g), and DPPH radical scavenging (IC50 = 2±0.003 mg/mL). Bahareh honey had the highest NO radical scavenging (IC50=0.0403±0.0009 mg/mL) and Meymand honey possessed the highest reducing potential by FRAP method (IC50=0.0018±0.000003 mg/mL). The maximum inhibition of α-glucosidase was shown in Meymand honey extract (46±0.1%). After sugar isolation, Zataria honey had the highest inhibition of α-glucosidase (54±0.6%) and the mode of α-amylase inhibition was noncompetitive by this honey. Whole extract (23±0.1%) and phenolic extract of Gavan honey presented the maximum inhibition of α-amylase (31.2±0.1%). Conclusion: Honey samples showed antioxidant potentials and anti-diabetic properties by retardation of α-amylase and α-glucosidase.

Oral versus intramuscular cholecalciferol replacement in hemodialysis patients with vitamin D deficiency

Introduction: Low 25-hydroxyvitamin D (25(OH)D) level in hemodialysis (HD) patients is associated with high bone turnover, secondary hyperparathyroidism, and decreased bone mineral density (BMD). Objective: To investigate the efficacy of equivalent doses of pulse oral cholecalciferol versus intramuscular (IM) cholecalciferol in correcting serum 25(OH)D levels in HD patients with vitamin D deficiency. Patients and Methods: In a prospective randomized open-label clinical trial, 80 HD patients with 25(OH)D level <20 ng/mL and serum intact parathyroid hormone (iPTH) level >100 pg/mL were enrolled in the study. Patients were divided into two groups. Group I: 40 HD patients received oral cholecalciferol 25 000 IU weekly for 12 weeks. Group II: 40 HD patients received a single dose of IM cholecalciferol 300 000 IU. Patients were maintained on their regular medications as alfacalcidol or phosphate binders. Serum calcium, phosphorus, 25(OH)D, alkaline phosphatase and iPTH were monitored at 0, 6th, and 12th week of intervention. Results: Significant increase in serum 25(OH)D level in group II patients who received IM (intramuscular) cholecalciferol, with delta mean a change of vitamin D level was 2.92 ±7.29 ng/mL over three months in comparison to the insignificant change in oral cholecalciferol group. Additionally there was a significant increase in the mean of serum calcium in comparison to oral cholecalciferol group, while we found a statistically significant decrease in alkaline phosphatase level in both groups too (P<0.05). The mean of iPTH levels was reduced significantly with IM cholecalciferol dose (1064.00 ± 787.60 to 609.9 ± 551.41 pg/mL; P<0.05). Conclusion: Intramuscular cholecalciferol dose is more effective at increasing 25(OH) D levels in dialysis patients than oral supplementation, achieves more increase in serum calcium and reduce iPTH levels. However, the longer duration of treatment is required to achieve recommended levels of vitamin D and suppress high iPTH levels.

Comparison efficacy of oral Nigella sativa seeds and tamsulosin on pain relief and passage of 4 to 10 mm stones of kidney and ureter; a randomized clinical trial

Introduction: Urinary stones are the third most common urinary tract disease after urinary tract infections and prostate diseases. Objectives: The aim of this study was to compare efficacy of Nigella sativa seeds and tamsulosin on expulsion and pain relief of ureteral and renal stones smaller than 10 mm. Patients and Methods: In this randomized clinical trial study conducted from March 2018-2019, 80 patients over 18 years old with kidney and ureteral stones sized between 4 to 10 mm were assigned to two groups by the simple random sampling method. In group one, after performing ultrasonography and confirming the presence of 4 to 10 mm stones, one 0.4 mg capsule of tamsulosin was prescribed each night for two weeks. In group 2, one gram of Nigellasativa prescribed every 12 hours after each meal with a glass of water for two weeks. After 2 weeks, patients were visited while a urinary tract sonography was conducted and the modification in size of stones and the existence of residual stones were measured and noted. The pain severity was measured through the visual analog scale (VSA). Data was gathered and analyzed throughout treatment and at the end of the study by the SPSS version 21 software, chi-square and independent t tests. Results: Mean sizes of stones before treatment with Nigella versus tamsulosin groups were 10.3±1.81 and 9.41 ± 1.68 mm respectively (P=0.06). Mean size of stones after treatment with Nigella versus tamsulosin groups were 4.97±4.33 and 5.21 ± 3.63 mm respectively (P=0.39). There was no significant difference between two groups regarding average of the pain score after treatment (P=0.05), but after intervention this score significantly declined in both groups, indicating more substantial in Nigella sativa group (P=0.001). Efficacy of treatment in Nigella and tamsulosin groups was 78.5 and 61.6, respectively (P=0.005). Conclusion: The present study indicated that both Nigella sativa seed and tamsulosin reduce urinary stone size and numbers without significant difference, however stone passage and pain control was more in the group of Nigella sativa. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trial (identifier: IRCT20081011001323N23; https://irct.ir/user/trial/35993/, ethical code; IR.YUMS.REC.1397.155).