Polycystic Kidney Disease

Introduction

Polycystic kidney disease is a genetic disorder causing the growth of multiple cysts that can impair renal function. Its clinical manifestations can be remembered with the ETHICAL mnemonic, which tells you it can present with worsening eGFR, tender flanks and hypertension whiles its main complications include intracranial aneurysms, cardiac disease, abdominal hernias, and liver cysts.

Based on its pathogenesis, it can be classified into two types: autosomal-recessive PKD and autosomal-dominant PKD.

The recessive disease is rarer and mostly affects the paediatric population.

Autosomal dominant PKD is more common, typically has an adult onset and is the focus of this video.

The dominant version is caused by a mutation in the PKD1 gene or in the PKD2 gene. 80% of people have PKD 1 mutations and conveniently, 2 goes with 2 so 20% have PKD2.

These genes code for polycystin 1 or 2 which are membrane proteins found in nearly all renal tubular cells, specifically on their cilium, which are hairlike projections. These proteins function as mechanoreceptors which help to inhibit cellular proliferation.

When they dysfunction, you get uncontrolled cell turnover and fluid build-up causing cysts. As they grow, the surrounding normal tissue is damaged and progressively compressed.

We can manage PDK through lifestyle optimisation, strict blood pressure control, specific disease modifying drugs, and complication treatment.

Healthy lifestyle choices are vitals and include

Smoking cessation
Weight optimisation and
regular exercise

Good blood pressure control

reduces the progression of renal disease and risk of cardiovascular complications.
In patients with early-stage disease, the recommended target is about 120/70 mmHg. Although guidelines vary based on country and disease stage.
Either ACE inhibitors or angiotensin receptor blockers are the first-line drug classes to consider in PKD induced hypertension

Disease modifying agents are relatively new treatment options

As ADH augments kidney cyst growth
Tolvaptan, which is an ADH antagonist, is indicated in patients with a
high risk of developing kidney failure

Complications should be investigated and treated appropriately.

Chronic flank pain is often overlooked by healthcare providers so always ask!
Watch out for intracranial aneurysms but remember small ones less than 7mm are usually managed conservatively
Finally, renal transplantation is the treatment of choice for ESKD

Let’s breakdown my ETHICAL mnemonic to understand the renal and extra renal features of PKD.

E stands for eGFR.

Over time renal function declines.
The onset and extent of this failure has massive variability between families and even within families.
However, males usually have a more rapid progression.

T stands for tender flanks. Pain can come from three causes:

Kidney stones, which is more common in PKD
Infection, either from pyelonephritis or infected cysts, or finally,
rupturing cyst which can cause massive haemturia.

H is for hypertension.

In general, cardiovascular dysfunction is the major cause of mortality in PKD.
Hypertension occurs before any reduction in GFR
And is probably caused by an increased activation of the renin-angiotensin-aldosterone system

Now the rest of this mnemonic works really well because you’ll remember the extra renal complications from least common to most.

I stands for intracranial aneurysms.

These are present in 10% of patients and occur because dysfunctional polycystin also causes defects in arterial muscle cells.

C is for cardiac disease.

This occurs in 20% of patients, which you can remember by doubling 10%.
Valvular disease is often how this manifests, especially Mitral valve prolapse.

A stands for abdominal wall hernias.

This occurs in 40% of patients, which you can remember by doubling 20.
This mostly manifests as Inguinal and paraumbilical hernias.

Finally, L stands for Liver cysts.

Polycystic liver disease eventually occurs in 80% of patients, which you can remember by doubling 40.

These are more common in women because
Oestrogen receptors are expressed in the epithelial lining of the cysts

I also want you to remember the rough rule of three 50s. It has a mean onset of symptoms at 50 years old, 50% of patients get end stage kidney disease yet only 50% of people find out they have it.

PKD is the ETHICAL disease presenting with worsening eGFR, tender flanks and hypertension and its main complications include intracranial aneurysms, cardiac disease, abdominal hernias, and liver cysts.

To remember our management, use this mnemonic to increase a patient’s lifespan. Make them a Sportsman, give them a SARTAN for their bloodpressure, then Tolvaptan and consider a renal transplant.