PKD Research: Targeting New Disease Pathways, Explaining Kidney Disease Symptoms and Tests

PKD Research

From Oxford University Press

Targeting new cellular disease pathways in autosomal dominant polycystic kidney disease


Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage renal failure. Understanding the molecular and cellular pathogenesis of ADPKD could help to identify new targets for treatment. The classic cellular cystic phenotype includes changes in proliferation, apoptosis, fluid secretion, extracellular matrix and cilia function. However, recent research, suggests that the cellular cystic phenotype could be broader and that changes, such as altered metabolism, autophagy, inflammation, oxidative stress and epigenetic modification, could play important roles in the processes of cyst initiation, cyst growth or disease progression. Here we review these newer cellular pathways, describe evidence for their possible links to cystic pathogenesis or different stages of disease and discuss the options for developing novel treatments.

Living with PKD

From Middle East North Africa Financial News (MENAFN)

Explainer: what is chronic kidney disease and why are one in three at risk of this silent killer?

A 42-year-old man – a father, a husband, a son – has come to the emergency department with a splitting headache. It's been there for months, slowly getting worse. Today it's unbearable.

He has no significant past medical history to explain the headaches and takes no regular medications. But he smokes and his is sky high – 210/100 mmHg (good blood pressure is 120/80 mmHg).

A series of investigations including blood and urine tests reveal significant kidney damage – stage four chronic kidney disease. Stage five kidney disease would mean he needs dialysis or a kidney transplant. This is serious.

Kidney disease is silent. Currently have evidence of chronic kidney disease, with many unaware of it. It's not of kidney function is lost that symptoms become apparent.

While symptoms like nausea, loss of appetite, lethargy and poor concentration are hallmarks of kidney failure, they are quite non-specific. Most people will have had these symptoms at some stage.

Fluid retention - swollen ankles and puffiness around the eyes - can be a marker of kidney disease. That's because the kidneys are key to regulating fluid in the body and a diseased kidney cannot do that as efficiently.

Using a blood and urine test. The blood test (serum electrolyes) gives you a 'percent of kidney function'. And the urine test (urinanalysis) tests for blood and protein in the urine, markers of damage and inflammation.What happens when your kidneys don't work well?

Kidneys are responsible for removing fluid and waste from your body that accumulate each day.

But when kidney function declines, fluid accumulates in the body. So, your legs can swell, and fluid can build up in the lungs, making it difficult to breathe.

Impaired kidneys also mean you cannot efficiently get rid of waste products, so these accumulate too. Such toxins in the body account for much of the symptoms of fatigue, nausea and loss of appetite.

Loss of kidney function and the build-up of fluid may lead to high blood pressure, which in turn may further speed up decline in kidney function. High pressures pulsating through the kidney damages their delicate filters and cause scar tissue to form.Loss of kidney function can lead to high blood pressure, which in turn can further speed up kidney disease.

People with chronic kidney disease are more likely to die from a heart attack or stroke. So, many people will die from heart disease before reaching end-stage kidney disease, the final stage of chronic kidney disease in which the kidneys no longer function well enough to meet your body's daily needs.

When healthy, kidneys secrete the hormone erythropoietin (or EPO), which stimulates red blood cells to form. But as kidney function declines, production of this hormone is impaired and anaemia (a low red blood cell count), follows. So, patients need to be injected with EPO to restore their red blood cell count.

The kidneys are also pivotal in maintaining calcium and phosphate levels in the blood. As phosphate builds up, severe itchiness can develop; calcium levels drop and, without attention, this can lead to fragile bones.Who is at risk?

Kidney disease is related to and caused by a number of different factors and conditions. As many as have at least one risk factor for chronic kidney disease.

Indigenous Australians are at risk with this risk increasing the more remotely they live. People with a family history of kidney disease are particularly vulnerable to it. Diabetes, high blood pressure, smoking, obesity, high cholesterol, heart disease, stroke and being over 60 are additional risks.

The number of people with chronic (long-term) kidney disease is forecast to increase by , largely due to diabetes and obesity becoming more common.

Anyone who has had an episode of acute kidney injury is also at risk of later developing chronic kidney disease. {Read more]