Investigating a novel treatment for nephrotic syndrome and diabetic nephropathy

11 July 2022

Imagine being on a course of treatment and tolerating the many side effects for weeks only to find that the treatment has been futile. This is the scenario facing up to 20% of patients with steroid resistant nephrotic syndrome (NS). Steroids aren’t always effective in treating NS and even when they are they come with a barrage of side effects. We need to think of new ways of treating NS, to make life easier for all patients and stop exposing them to horrible side effects.

The problem

NS is a condition where the kidneys don’t work properly. They leak protein into the urine making people feel unwell. If left untreated the condition can advance to end-stage renal failure (ESRF). This condition can be genetic or non-genetic. We don’t really know exactly what causes the non-genetic form, though we have a few good ideas.

Currently patients are treated with steroids. Around 20% of non-genetic nephrotic syndrome will be resistant to steroid treatment. Without effective treatment their kidney function could rapidly decline leading to dialysis and transplant. Some patients will initially respond to steroid treatment only to later become steroid resistant. Even for those who respond well to steroid therapy, the side effects such as obesity, high blood pressure, poor growth, diabetes, and osteoporosis are all well documented. Clearly, we need a better treatment.

Put a pin in it

Dr Carl May and his colleagues at Bristol Renal have identified a mechanism for how nephrotic syndrome might be working and think they know how to block it.

Cells are always trying to adapt to their environment. Sometimes they receive bad messages from their environment that they would be better off ignoring.

Imagine if a message was delivered to a cell by unlocking and opening a door. The bad guy unlocks the door and delivers an unhelpful message. Even if the bad guy has a key, we can stop them getting in by the leaving our key in the lock on our side of the door. The bad guy can’t get in, the unhelpful message is not delivered.

This is what Carl intends to do. Carl and his colleagues can arm a cell with a small hairpin that can stop this particular message being delivered to the cell. This door is the same door that lets a lot of the damage caused in diabetic nephropathy in. Blocking this door could protect kidney function in type 2 diabetes.

Dr Carl May

What this might mean for kidney patients?

This work could lead to a treatment that is effective for all non-genetic forms of ns. There would be no need to think of patients with NS as being steroid sensitive or steroid resistant. This treatment is completely different to steroid therapy and will theoretically be side-effect free. Patients won’t have to be exposed to long courses of steroid treatment, enduring the side effects only to find out that their form of NS is steroid resistant. Currently treatment for diabetic nephropathy is limited to controlling blood sugar and hoping that kidney function doesn’t decline too much. This work could actively protect kidney function during periods of poor blood sugar control.

What does this funding mean for me and my career?

Carl said: “This is the first time that I have secured funding in my own right. I am at a stage in my career where I am looking to branch out and become more independent. So, I will use this grant to test my ideas and gain data for a fellowship application. My PhD studentship was funded by Kidney Research UK, since then, through the alumni network, I have received lots of guidance and support from the charity. Kidney Research UK is so much more than a funder for young scientists. The environment they provide for us is very nurturing. I am delighted to have received this funding.”

“I would like to thank Kidney Research UK for this award. The funding is vital not only to research new treatments for nephrotic syndrome but also to help me pursue my career as a renal scientist. Kidney Research UK is so much more than a funder. Everyone I have interacted with at the charity is always available for help and advice. This is very much appreciated!”