Jinil Yoo*, Hugo Villanueva

Division of Nephrology, Montefiore Medical Center – Albert Einstein College of Medicine, Bronx, NY, USA

Lupus nephritis (LN), a common and serious complication of systemic lupus erythematosus (SLE) is considered as a typical immune-complex mediated disease, and currently classified into 6 classes, primarily based on histologic findings of glomerular involvement, which became accepted worldwide for diagnosis, prognosis, and treatment guide. In recent years, a rising numbers of cases are reported to have a nonimmune complex-mediated glomerular podocytopathy among SLE patients presenting with nephrotic syndrome. The kidney biopsy done in those patients showed some with minimal change disease-like features, some with mesangial proliferation and some with focal segmental glomerulosclerosis on light microscopy (LM), but all with diffuse foot process effacement (FPE), and no glomerular capillary proliferation/inflammation on LM as seen in class lll and IV LN and no glomerular capillary immune deposits on immunofluorescence (IF) study, observed in class V LN, suggestive of podocyte injury caused by a nonimmune complex mediated pathway, called as “lupus podocytopathy”. Although it is not accepted as a class of LN, the case of lupus podocytopathy of non-immune complex origin is growing and emerging as a distinct entity, of active lupus nephritis, since lupus podocytopathy usually occurs concurrently with extrarenal and active serologic activity, and mostly within 6 months of SLE onset.

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Marta Ligero1, Kinga Bernatowicz1, Raquel Perez-Lopez1,2*

Radiomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, 08035, Spain

Radiology Department, Vall d’Hebron University Hospital, Barcelona, 08035, Spain

*M.L. and K.B. are joint first authors. They have contributed equally to the literature systematic review and drafting of the manuscript.

The application of advanced computational analysis to medical imaging opens a plethora of opportunities in the field of radiology, allowing for more accurate tissue characterization and, eventually, advancing towards precision medicine through imaging biomarkers. In this review, we briefly introduce the methodology for radiomics analysis and the main challenges for implementation of radiomics-based tools in clinical practice. Based on systematic review of published studies, we also summarize here the main advances regarding CT-based radiomics applications in renal cancer with regards to tumor characterization (diagnosis, grading, prognosis), gene expression prediction (radiogenomics) and response evaluation.

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Issaka Yougbare

Systemic lupus erythematosus (SLE) is an autoimmune disease with a broad spectrum of clinical manifestations, but its pathogenesis remains fairly understood. Cyclic nucleotide signaling pathways in immune cells and kidney are emerging as cellular mechanisms governing SLE disease progression. Upregulations of cGMP/cAMP metabolism lead to lupus nephritis and abnormal kidney remodeling/hypertrophy. PDE4 family remains the major cAMP hydrolyzing enzyme as PDE1 is responsible for cGMP breakdown in kidney. SLE disease progression to lupus nephritis is correlated with increase PDE1 and PDE4 activities resulting in lower cyclic nucleotide levels in kidney. Administration of Nimodipine, a PDE1 inhibitor prevents the lymphoproliferative phenotype and exert anti-proliferative effects on mesangial cells while PDE4 inhibitor NCS 613 prevents inflammatory cytokines release, immune complex deposition, and nephritis in MRL/lpr lupus prone mice. In this review, we highlight recent findings of alterations of cyclic nucleotide signaling pathways in lupus nephritis. Given the role of cAMP/cGMP signaling in kidney function, dual inhibition of PDE1 and PDE4 may represent a promising therapeutic approach to tackle lupus nephritis.

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Sin Sil Ha1, Kazi Rubaina1,2, Chung-Shien Lee1,2, Veena John2, Nagashree Seetharamu2*

1St. John’s University, College of Pharmacy and Health Sciences, Department of Clinical Health Professions, 8000 Utopia Parkway, Queens, NY 11439, USA.

2Division of Medical Oncology and Hematology, Northwell Health Cancer Institute, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, 450 Lakeville Road, Lake Success, NY 11042, USA

Despite reports of amifostine possibly protecting nephrotoxicity from cisplatin, it has not been recommended by any guidelines committees or routinely prescribed in clinical practice over the past decade. In this article, we review literature and guidelines regarding use of amifostine in oncology practice for protection against adverse effects from certain chemotherapeutic agents, in particular as a nephro-protectant in patients receiving cisplatin.

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Charles Taylor1*, Brian Birch1,2

1University of Southampton, Faculty of Medicine

2University Hospitals Southampton NHS FT, Southampton, UK

3Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

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Sabrina R. Gonsalez1, Aline L. Cortes1, Mayara A. Romanelli1, Paula Mattos-Silva2, Andrew C. Curnow3, Minolfa C. Prieto3,4, Marcelo Einicker-Lamas2, Lucienne S. Lara1

1Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

2Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

3Department of Physiology, School of Medicine, Tulane University School of Medicine, New Orleans, LA, USA

4Tulane Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA, USA

Lysophosphatidic acid (LPA) protects the kidneys from tissue ischemic reperfusion injury (IRI), but its impact on renal function is primarily limited to glomerular function. We estimated the status of renal function by a complete glomerular and tubular functional analysis to test the hypothesis that LPA treatment during ischemia-reperfusion (I/R) protects renal function by attenuating IRI. Male Wistar rats were subjected to bilateral kidney I/R. Along with ischemia, LPA was administered. LPA increased levels of plasma LPA, downregulated LPA2R, prevented interstitial fibronectin and TGF-β1 accumulation, and prevented a decrease in glomerular filtration rate (GFR). I/R increased urine volume and proteinuria and decreased fractional Na+ excretion (FENa) and urine osmolality. These effects were not prevented by LPA. The reduction in FENa was attributed to disruption in tubular Na+ transport and downregulation of protein kinase C (PKC) activity. LPA treatment maintained (Na++K+)ATPase activity to the control level, due to a sustained sensitivity to PLC/PKC pathway. Na+-ATPase activity was insensitivity to LPA treatment. This ineffectiveness was associated with downregulation of LPA2R, resulting in low FENa. Altogether, LPA treatment maintained normal kidney structure and prevented the reduction of glomerular function. However, even in the setting of preserved GFR, impaired tubular function may present a high risk for silent progression of kidney disease.

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Derick S Alves1, Fabiana Elias2, Helvécio L S Junior3, Guilherme Thizen3, Rômulo S A Eloi4, Carlos E Fonseca-Alves1*

1Institute of Health Science, Paulista University – UNIP, Bauru – SP, Brazil.

2Universidade Federal da Fronteira Sul (UFFS), Realeza, PR, Brazil.

3Departamento de Medicina Veterinária, Faculdade UPIS, Brasília, DF - Brazil.

4HistoPato-Análise Anatomopatológica Veterinária, Brasília, DF, Brazil.

Urinary bladder cancer is uncommon in dogs, corresponding to 1% of all reported canine malignancies. Smooth muscle neoplasms can be benign (leiomyomas) or malignant (leiomyosarcoma) and are rare in humans and animals. As the incidence of urinary bladder leiomyosarcoma in dogs is low, our report presents the clinical and pathological aspects of primary urinary bladder leiomyosarcoma in a dog. A 10-year-old boxer breed dog was referred to the veterinary hospital presenting with dysuria for a month, appetite loss for seven days, abdominal distension for two weeks, and anuria for the last three days. After a physical examination and laboratory tests, an abdominal mass was diagnosed, and a laparotomy was performed. During the surgery, it was found that the urinary bladder neoplasm occupied the bladder trigone region, involving the ureters, and causing obstruction. The urinary bladder was reconstructed successfully, and the patient was kept under post-operative evaluation. In the post-operative recovery, an acute kidney disease was observed, which was irresponsive to the clinical treatment. Due to the advanced stage of the disease and the non-response to treatment, euthanasia was performed after surgery, and the animal was sent for necropsy. In this case, leiomyosarcoma was manifested as an expansive, low infiltration, and non-metastatic disease, causing obstruction of the ureters and consequent hydronephrosis.

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Nawar M. Shara, PhD1,2,3*, Sameer Desale, MS1, Barbara V. Howard, PhD1,2,3, Zeid Diab1,4, Wm. James Howard, MD5, Lyle G. Best, MD6, Wenyu Wang, PhD7, Elisa T. Lee, PhD7, Richard B. Devereux, MD8, Xiyao Ai, MS9, Jason G. Umans, MD, PhD1,2,3

1 MedStar Health Research Institute, Hyattsville, MD, United States.

2 Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, United States.

3 Georgetown University, Washington, DC, United States.

4 Virginia Commonwealth University, Richmond, VA, United States.

5 MedStar Washington Hospital Center, Washington, DC, United States.

6 Missouri Breaks Industries Research Inc., Eagle Butte, SD, United States.

7 College of Public Health, University of Oklahoma, Oklahoma City, OK, United States.

8 Weill Cornell Medicine, New York, NY, United States.

9 American University, Washington, DC, United States.

American Indians (AI) have a high prevalence of diabetes, obesity, cardiovascular disease (CVD), and chronic kidney disease. Inclusion of kidney function and other population-specific characteristics in equations used to predict atherosclerotic CVD (ASCVD) risk may help define risk more accurately in populations with these chronic diseases. We used data from the Strong Heart Study (SHS), a population-based longitudinal cohort study of AI, to modify the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort ASCVD risk equations and then explored the performance of the new equations in predicting ASCVD in AI. The study included baseline SHS exam data from 4213 individuals between 45 and 75 years of age, collected in 13 communities from 3 geographic areas in the United States and spanning a wide range of tribal backgrounds, with continuous follow-up data from 1989 to 2015. Using SHS data for blood pressure, diabetes, cholesterol, smoking, and renal function, Cox proportional hazard models were developed to predict ASCVD-free time for AI men and women. ASCVD risk in AI calculated using the SHS-modified equations were compared to risk calculated using the ACC/AHA pooled cohort equations for African Americans (AAs) and Whites. Goodness-of-fit measures for ASCVD risk prediction showed that the SHS-modified equations fit the data from the SHS better than the ACC/AHA equations for AAs and Whites. Adjusting risk prediction equations using population data from the SHS and including measures of renal function significantly improved ASCVD risk prediction in our AI cohort.

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Mansoor N Ali

Consultant Nephrologist, Renal Unit, Department of Renal Medicine, St. Luke’s Hospital, Bradford Teaching Hospitals NHS Foundation Trust, BD5 0NA

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Francis Lemire1, Anne-Sophie Blais1, Katherine Moore1 and Stephane Bolduc1*

1Division of Urology, Department of Surgery, CHU de Québec - Université Laval Research Center, Québec, Canada

Purpose of the review: Vesicoureteral reflux (VUR) is a common pathology encountered in pediatric urology. If left untreated, this condition can lead to infectious complications, hypertension and loss of renal function by scars. There is a trend for minimally invasive procedures to minimise treatment-related complications. Endoscopic subureteral injection of bulking agent in the treatment of VUR is an example of minimally invasive options. Several bulking agents have been studied and the perfect agent has not yet been discovered. Polyacrylamide hydrogel is a relatively new agent used to treat VUR and its use will be reviewed.

Recent findings: Three modern studies from a Canadian group have evaluated the use of polyacrylamide hydrogel for endoscopic injection to treat VUR. The first study reported a cure rate of 81.2% without major complication. In the second study, injection of polyacrylamide hydrogel was compared to dextranomer hyaluronic acid and no significant difference was observed, with overall success rate of 73.1% and 77.5% respectively. The third trial evaluated the long-term efficacy and safety of polyacrylamide hydrogel with a 36-month follow-up. Overall success at 3 months was 70.7% and no patient had de novo hydronephrosis or calcification of the agent at 36 months.

Conclusion: Polyacrylamide hydrogel seems to be a safe and effective alternative bulking agent in the treatment of VUR. The contribution from other centers to validate those data would be valuable.

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Beuy Joob 1*, Viroj Wiwanitkit 1

1Sanitation 1 Medical Academic Center, Bangkok Thailand

1Honorary professor, dr. DY Patil University, Pune, India

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