Pharmacy - Modified Ponticelli regime

This leaflet will provide you with information about the Modified Ponticelli regimen.

What is the Modified Ponticelli regimen?

The Modified Ponticelli regimen is a combination of drug treatments used in treating a kidney disease called membranous nephropathy. The Modified Ponticelli regimen is named after Professor Claudio Ponticelli, an Italian doctor, who first demonstrated that it was effective in treating some people with membranous nephropathy. It is a 6-month treatment to dampen (or lower) your immune system.

In the Modified Ponticelli regimen, you will be given the following treatments:

• A steroid called methylprednisolone (as an infusion)
• Steroid tablets (called prednisolone)
• Cyclophosphamide tablets (a type of chemotherapy medication)

More details about these treatments are given in later sections of this leaflet.

Why has my doctor recommended this treatment?

The Modified Ponticelli regimen is given to people with membranous nephropathy whose condition is unlikely to get better without medication to dampen their immune system. If high levels of protein leak continue, patients with membranous nephropathy are at risk of kidney decline and potentially kidney failure (35-50% risk by 10 years). The decision to start this treatment will be made by your kidney doctor after discussion with you.

What does the Modified Ponticelli regimen involve?

Your treatment will be given to you over a 6-month period. In the first month you will be given steroids and in the second month you will be given tablets called cyclophosphamide. This two-month cycle is then repeated three time in total over 6 months.

Steroids: For the first three days at the start of every month of steroid treatment (months one, three and five) you will need a steroid drip/infusion through a cannula (small plastic tube) into a vein in your hand, which takes about an hour. This will be given to you in our outpatient setting. If you would like to, you can have a friend or relative stay with you.

On the third day, you will be given a supply of the steroid tablet, to take for the rest of the month, starting from the next day. We will give you the cyclophosphamide tablets at your follow-up clinic appointment once you have completed the steroid tablets.

Month 1,3 and 5: Steroids

On days one, two and three you will come to Salford Royal for the steroid infusion. Day 4 onwards for the rest of the calendar month take steroid tablets.

Month 2,4 and 6: Cyclophosphamide

This is an immunosuppression tablet to be taken for the full calendar month. Weekly blood tests are needed to check your blood count has not been affected.

It is very important to attend your blood test appointments.

Cyclophosphamide should be taken in the morning, so that your body processes it throughout the day. It is best taken on an empty stomach but can be taken with food if you find it makes you feel sick.

You will also be given the following medications to take for the whole 6 months of treatment:

• Antibiotics, such as co-trimoxazole. These help to protect against certain lung infections
• Omeprazole or other medication to reduce the amount of acid in your stomach and protect your stomach lining *
• Some tablets to protect your bones, such as Alendronic acid, calcium and vitamin D supplements *

These medicines help to reduce some of the side effects of the treatment.

*You do not have to take this during the months you are having cyclophosphamide

What are the benefits of the treatment?

In research studies, people with membranous nephropathy who are treated with the Modified Ponticelli regimen have less protein in their urine (an important marker of kidney damage) and are less likely to develop kidney failure.

What are the side effects?

Steroids: Steroids can cause side effects, but most people find they can cope with these for the short period of time they are taking the treatment. These side effects are normally short lived. The following is a list of more common side effects you may experience:

• A change in your sleep pattern, normally difficulty falling asleep. Taking the tablets in the morning should help with this
• A change in your mood (feeling more up or down)
• Upset stomach including feeling sick
• Heart burn or indigestion
• Increased risk of stomach ulcers
• A metallic taste in your mouth
• An increased appetite
• Weight gain - this is usually short term
• A round appearance of your face
• Fluid retention, ankle swelling and increased blood pressure. Your doctor will check your blood pressure
• Increased risk of infection
• Diabetes we can provide you with a monitor to check your blood sugar regularly at home
• Thinning of the bones (osteoporosis)
• Changes in your eyesight due to conditions like glaucoma and cataracts

If you are diabetic, you might find your blood sugar levels will be higher, so we will advise you to measure your blood sugars more frequently. Your treatment for diabetes may need to be adjusted.
 
Very rarely, some people can experience severe damage to their hip (known as avascular necrosis of the hip).

Cyclophosphamide: common short-term side effects of cyclophosphamide include:

• Low white blood cell count (this can increase your risk of infection). Therefore, blood test monitoring is very important
• Feeling sick or being sick let us know if this is a problem as anti-sickness tablets can help
• Irritation of the lining of the bladder and blood in the urine. Tell your doctor straight away if this happens. To reduce the risk of this happening, you should drink 8-10 glasses (2-3 litres) of water and/or non-alcoholic drinks a day

Occasional side effects of cyclophosphamide include:

• Hair loss (usually grows back after stopping the drug)
• Diarrhoea
• Mouth ulcers - Mouthwashes can help, for example, chlorhexidine
• A sore red mouth can occur. This can be prevented with miconazole or nystatin taken four times a day
• Skin changes Skin may darken, but this is rare
• Low platelet count (this can cause unexplained bruising or bleeding)

Cyclophosphamide can also cause:

• Infertility - This is unlikely to occur with only three months of treatment, but you should discuss this further with your kidney doctor
• Damage to an unborn child - Men or women who are taking cyclophosphamide should not try for a baby
• Cancer (including bladder cancer) - Cyclophosphamide causes a small increase in the risk of some cancers. Your healthcare team will give you more information about this

If you develop a high temperature whilst on the Modified Ponticelli regimen, please contact the Renal team or come to A&E and tell the doctors and nurses that you are receiving prednisolone or cyclophosphamide under the renal team.

How will I be monitored during treatment?

You will be seen every two to four weeks in the renal clinic during treatment. During the months you are receiving cyclophosphamide you will need more frequent blood tests to monitor your blood count. Please plan with your kidney team where these blood tests will be done so they know where to look for the results.

What happens after my treatment?

After you have finished the course of treatment, your kidney doctor will review with you the results of your response to the treatment. This is done by measuring the leftover amount of protein in your urine and whether your kidney function has improved or stabilised, compared with before.

If you no longer have any significant protein leak (urine PCR less than 30) you are in complete remission.

If the protein leak has halved and urine PCR is now less than 350, you have achieved a partial remission.

Patients who achieve complete or partial remission have an 80-90% chance of avoiding kidney failure within 10 years.

If you have not responded initially, you can sometimes see a delayed improvement over the next six months. However, if the membranous nephropathy persists thereafter or is getting worse, further treatment options will be considered in clinic with your doctors.

Please note that the doses of immunosuppression can change depending on the blood results (for example, in the case of cytopenia).

Further information

The following website has useful information about the treatment of membranous nephropathy:

National Kidney Foundation: www.kidney.org.uk

The Renal Association: www.rarerenal.org

Contact telephone numbers
Renal Outpatients: 0161 206 1478

Reference

Adapted from East and North Hertfordshire Hospitals patient information: Ponticelli Treatment, November 2022.

Modified Ponticelli Regimen Medication Record

Name: ______________________________    

Hospital No: ____________________    

Month 1:
Methylprednisolone injections on days: __________________________________________________________________
Prednisolone tablets _____ mg each morning for 27 days.
To start __________ and end __________     

Month 2:
Oral cyclophosphamide tablets _____ mg daily.
To start __________ and end __________         
Frequent blood tests

Month 3:
Methylprednisolone injections on days: __________________________________________________________________
Prednisolone tablets _____ mg each morning for 27 days.
To start __________ and end __________     
 
Month 4:
Oral cyclophosphamide tablets _____ mg daily.
To start __________ and end __________           
Frequent blood tests

Month 5:
Methylprednisolone injections on days: ___________________________________________________________________
Prednisolone tablets _____ mg each morning for 27 days.
To start __________ and end __________     

Month 6:
Oral cyclophosphamide tablets _____ mg daily.
To start __________ and end __________ 
Frequent blood tests

My flu jab date: ____________________     

My pneumonia jab date: ____________________