Primary membranous nephropathy: comprehensive review and historical perspective.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in non-diabetic Caucasian adults over 40 years of age. It has an estimated incidence of 8-10 cases per 1 million. Fifty per cent of patients diagnosed with primary MN continue to have nephrotic syndrome and 30% of patients may progress to end-stage renal disease over 10 years. Although it was recognised as a distinct clinic-pathological entity in 1940s by immunofluorescence and electron microscopy, the pathogenesis and treatment have become more apparent only in the last decade. Discovery of M-type phospholipase A2 receptor (PLA2R) antibodies and thrombospondin type 1 domain-containing 7A antibodies has given new perspectives in understanding the pathogenesis of the disease process. Anti-PLA2R antibody is the first serologic marker that has promising evidence to be used as a tool to prognosticate the course of the disease. More importantly, therapeutic agents such as rituximab and adrenocorticotropic hormone analogues are the newer therapeutic options that should be considered in the therapy of primary MN.

Diabetic nephropathy: newer therapeutic perspectives.

Diabetic nephropathy (DN is a dreaded consequence of diabetes mellitus, accounting for about 40% of end-stage renal disease (ESRD). It is responsible for significant morbidity and mortality, both directly by causing ESRD and indirectly by increasing cardiovascular risk. Extensive research in this field has thrown light on multiple pathways that can be pharmacologically targeted, to control or reverse the process of DN. Glomerulocentric approach of DN still continues to produce favourable results as evidenced by the recent data on SGLT-2 (sodium glucose co-transporter type 2) inhibitors. Beyond the glomerular mechanisms, numerous novel pathways have been discovered in the last decade. Some of these pathways target inflammatory and oxidative damage, while the others target more specific mechanisms such as AGE-RAGE (advanced glycation end products-receptors for advanced glycation end products), ASK (apoptotic signal-regulating kinase), and endothelin-associated pathways. As a result of the research, a handful of clinically relevant drugs have made it to the human trials which have been elucidated in the following review, bearing in the mind that there are many more to come over the next few years. Ongoing research is expected to inform the clinicians regarding the use of the newer drugs in DN. Abbreviations: USFDA: Unites States Food and Drug Administration; SGLT-2: Sodium glucose transporter type 2; GLP-1: Glucagon-like peptide-1; DDP-4: Dipeptidyl peptidase-4; UACR: urinary albumin creatinine ratio; eGFR: Estimated glomerular filtration rate; CKD: Chronic kidney disease; DN: Diabetic nephropathy; TGF: Tubuloglomerular feedback; RAAS: Renin angiotensin aldosterone system; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; RCT: Randomized controlled trial; AGE-RAGE: Advanced glycation end products-receptors for advanced glycation end products; ASK-1: Apoptotic signal-regulating kinase-1; Nrf-2: Nuclear 1 factor [erythroid derived-2]-related factor 2; ml/min/1.73m2: Millilitre/minute/1.73 square meters of body surface area; ~: Approximately.

Urinary exosomal expression of activator of G protein signaling 3 in polycystic kidney disease.

OBJECTIVE: PKD is a genetic disease that is characterized by abnormally proliferative epithelial cells in the kidney and liver. Urinary exosomes have been previously examined as a source of unique proteins that may be used to diagnose and monitor the progression of PKD. Previous studies by our group have shown that AGS3, which is a receptor-independent regulator G-proteins, was markedly upregulated in RTECs during kidney injury including PKD. In this study, our goal was to determine whether AGS3 could be measured in exosomes using animals and humans with PKD. RESULTS: In our study, urinary exosomes were isolated from PCK rats and the control Sprague-Dawley (SD) rats. AGS3 expression was significantly increased (P < 0.05) in PKD versus SD rats at 16 weeks of age. This increase was detectable in a time-dependent manner from 8 weeks of age and peaked at ~ 16-20 weeks (length of study). Similarly, in exosomes from human urine samples with PKD, AGS3 expression was significantly increased (P < 0.05) compared to healthy human controls where AGS3 was largely undetectable. In conclusion, the detection of AGS3 in urinary exosomes may be a novel biomarker for PKD, and provide new insight into the biology of tubular epithelial cell function during cystic disease progression.