Multi-Target Drugs for Kidney Diseases

Kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), and glomerular nephritis can lead to dialysis and the need for kidney transplantation. The pathologies for kidney diseases are extremely complex, progress at different rates, and involve several cell types and cell-signaling pathways. Complex kidney diseases require therapeutics that can act on multiple targets. In the past ten years, in silico design of drugs has allowed for multi-target drugs to go quickly from concept to reality. Several multi-target drugs have been successfully made that target arachidonic acid pathways and transcription factors to treat inflammatory, fibrotic, and metabolic diseases. Multi-target drugs have also demonstrated great potential to treat diabetic nephropathy and fibrotic kidney disease. These drugs act by decreasing renal transforming growth factor-β (TGF-β) signaling, inflammation, mitochondrial dysfunction, and oxidative stress. There are several other recently developed multi-target drugs that have yet to be tested for their ability to combat kidney diseases. Overall, there is excellent potential for multi-target drugs that act on several cell types and signaling pathways to treat kidney diseases.

Clinicopathological Outcome in Infection Related Glomerulonephritis

Background: The term infection-related glomerulonephritis (IRGN) was proposed as the streptococcal, staphylococcal and gram-negative organisms were being isolated among elderly and immunocompromised patients treated for glomerulonephritis. Previously these were called as Post-infectious glomerulonephritis (PIGN). Most of the reported patients were Caucasians and Asians with male predominance. Among the adult IRGN patients a kidney biopsy is recommended to confirm the diagnosis and to rule out other glomerulonephritis. Aims & Objectives: To study the clinical characteristics and pathological patterns of infection-related glomerulonephritis (IRGN) in adults and to assess the clinical and pathological differences of C3 dominant and codominant IRGN patients. Subjects and Methods: A hospital-based, analytical retrospective clinical study was conducted among seventy-three patients. Cases were included irrespective of gender with biopsy proven IRGN and aged equal to or greater than 18 years of age. The study was conducted for a period of 6 months from 1st June 2019 to 30th Nov 2019 at Sapthagiri Institute of Medical Sciences and Research Center, Bangalore. A prior permission from the institutional ethics committee and written consent from the patients and their family members were obtained. Data obtained was entered in Microsoft Excel-2013 and analyzed in SPSS version-22 trial. Appropriate statistical tests were applied and p-value less than 0.05 was considered as significant. Results: In the present study 73 patients were included based on the selection criteria. The mean age of the study population was 41.8 ± 14.5 years. Majority 51 p.c (37) of study population were males and 49 p.c (36) were females. Hypertension was the most common risk factor which was reported among 56 p.c (32) of the patients. Diabetes was reported among 17 p.c (10) of the patients. About 15 p.c (9) of the patients were alcoholics and 10 p.c (6) of the patients were smokers. Conclusion: Renal biopsy plays an important role in the assessment of prognosis and underlying glomerular nephritis (GN).

Bacillus cereus Subacute Native Valve Infective Endocarditis and Its Multiple Complications

Bacillus cereus causing infective endocarditis (IE) in a native valve is an extremely rare event, but it is reported mostly in intravenous drug abusers and other risk factors as immunosuppression, malignancy, and valvular heart disease including prosthetic heart valves. We report a case of B.cereus native mitral valve infective endocarditis in a 58-year-old Sri Lankan male who is not a drug abuser who presented with painless hematuria with reduced urine output. During hospital stay, he developed frequent episodes of brief focal seizures. He had undergone multiple investigations that revealed splenic abscesses, cerebral vasculitis, and glomerular nephritis with positive rheumatoid factor, cytoplasmic antineutrophil cytoplasmic antibody (C-ANCA), and cryoglobulin. The appropriate antibiotic was the prime therapeutic intervention which carried an excellent prognosis. This case highlights an unusual organism in the blood culture that caused IE warranting thorough physical examination and investigations.

P0748CLINICAL OUTCOMES OF JAPANESE ANTI-MYELOPEROXIDASE ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-RELATED RAPIDLY PROGRESSIVE GLOMERULAR NEPHRITIS

Background and Aims Anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-related nephritis constitutes 60% of rapidly progressive glomerular nephritis (RPGN). In 2014, Japanese Society of Nephrology (JSN) created RPGN clinical guidelines for Japanese MPO-ANCA-related RPGN patients, and proposed the clinical grading system for predicting their prognosis, which took into consideration factors such as age, renal function, lung involvement, and serum CRP (Yoshihiro Arimura et al. Clin Exp Nephrol. 2016). However, evidence regarding clinical outcomes is still limited. In the study reported here, we conducted a single-center retrospective study to evaluate the outcomes of MPO-ANCA-related RPGN patients and to establish an efficacy of RPGN guidelines of JSN. Method We retrospectively investigated 54 patients (female, n=32; average age ± 13.0 years) with MPO-ANCA-related nephritis. The patients were admitted to Fukuoka University Hospital between 2009 and 2018. Their clinical grade determined by JSN guideline and method of treatment were retrospectively evaluated for prediction of survival, as well as laboratory data and clinical features. Results 12 patients (22.2 %) has deceased during a median observation period of 17.1 months. 7 patients are died of infectious disease (Bacterial pneumonia 4, Sepsis 2, pulmonary aspergillosis 1), and 10 patients died within 1 year. Median estimated glomerular filtration rate (eGFR) was 15.5 mL/min/1.73m2 at admission. 14 patients (25.9%) presented with end-stage renal disease (ESRD) during the observation period, 8 of them were died. The distribution of clinical grade of JSN guideline was grade I for 10, II for 27, III for 10 and IV for 7. (grade IV is the most severe) Patients with high clinical grade showed significantly high mortality (Log Rank test, p<0.05; figure 1). Multivariate Cox proportional hazards model analysis revealed that high clinical grade was a significant risk factor for all-cause death (Hazard ratio (HR), 7.09; 95% confidence interval (CI), 2.01-15.69, p<0.05) and for infectious disease death (HR, 16.9; 95% CI, 2.56-121.5, p<0.05). On the other hands, the preventive administration of Trimethoprim-Sulfamethoxazole (TS) decreased the risk of infectious disease death (figure 2). Conclusion The MPO-ANCA-related RPGN clinical grading system created by JSN was a useful tool for prediction of prognosis. Furthermore, TS should be administrated for all immune-suppressive patients to prevent variable infections not only Pneumocystis.

Prospects for the use of chondroitin sulfate and glucosamine sulfate with osteoarthritis associated with pathology of the kidneys and urinary system

Introduction. Chondroitin sulfate (CS) and glucosamine sulfate (GS), widely used as chondroprotectors, can maintain the normal functioning of the urinary system but their effect has not been analyzed systematically.Aim: to perform a systematic analysis of the possibilities of using CS and GS in patients with pathology of the kidneys and urinary system.Materials and methods. Predictive analysis of 2,093 publications on the interactions of CS/GS with the functioning of the kidneys and other organs of the urinary system found at the request “(urinary OR bladder OR kidney) AND (glucosamine OR chondroitin)” by methods of the theory of topological data analysis.Results. Disorders of cholesterol and glucosamine metabolism are characteristic of cystitis, glomerular nephritis, urinary tract infections (UTIs), urolithiasis, proteinuria, and formation of diabetic nephropathy. In addition to inhibiting the pro-inflammatory cascade NF-kB, CS/GS contribute to eliminating the deficiency of glycosaminoglycans in the pathology of urothelium, inhibit urolithiasis, inhibit the synthesis of pro-inflammatory nitric oxide NO in macrophages, and modulate O-glycosylation processes.Conclusion. The results of fundamental and clinical studies show that subsidies of CS/GS substances of pharmacological quality per os and CS instillation in the bladder (in particular, in combination with hyaluronic acid) are the means of choice for patients suffering from osteoarthritis and diseases of the urinary system. Highly purified pharmacological CS substances are part of the preparation Chondroguard.

A FIBROUS CAVITY IN AN IMMUNOCOMPROMISED LUNG: NOCARDIOSIS MASQUERADING AS TUBERCULOSIS

Nocardia species can cause fulminant necrotizing cavitatory pneumonia. Diagnosis involves identification of the organism, speciation and correlating with appropriate clinical and radiological findings. Speciation is often difficult due to the complexities involved in culturing the organism. Treatment involves administering antibiotics for a prolonged duration. The authors hereby report a case of pulmonary Nocardiosis in a patient who had pre-morbidities like cirrhosis of liver and membrano-proliferative glomerular nephritis on immune-suppression with high dose corticosteroids making him vulnerable to the organism.