Autosomal dominant polycystic kidney disease and transplantation

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder affecting 1 in 1,000 people and responsible for 10% of cases of the end stage renal disease (ESRD). Apart from renal manifestations, changes in other organs may be present. In the absence of contraindications, patients with ADPKD and ESRD should be referred to renal transplantation. The ADPKD patient may also need liver transplantation, or combined liver and kidney transplantation. Also, the patient with ADPKD may become a potential organ donor. The aim of our paper is to review the problems that the physicians deal with in ADPKD patients in pre- and post-transplant period.

Figure 1. Cyst Development in Renal Tubules

In a cell that has one allele carrying the genetic mutation, a second “hit” to the normal allele propels perpetual proliferation, causing a bulge to form in the wall of the tubule. Further expansion is caused by cyclic AMP (cAMP), epidermal growth factor, and insulin-like growth factor. The cyst is in fact a benign renal tubular neoplasm that expands by increasing the mass of proliferating mural epithelial cells that surround a cavity filled with fluid. Cyst formation begins in utero and continues throughout life. The expanding cyst causes changes in the tubular basement membrane beneath it. Macrophages and fibroblasts, forerunners of fibrosis, appear in the interstitium. Most of the cysts that reach 2 mm in diameter have separated from the parent nephrons, becoming autonomous tumors as cellular proliferation and fluid secretion join to promote progressive enlargement; cAMP stimulates cyst growth by increasing the rate of cellular proliferation and by stimulating the rate of fluid secretion into the cysts.

Figure 2. Radiologic Features of Autosomal Dominant Polycystic Kidney Disease

Panel A shows paired T₁-weighted and T₂-weighted MRI scans from three patients with a normal glomerular filtration rate (GFR) but different stages of disease progression. The T₁-weighted images (top row) were obtained after intravenous infusion of gadolinium to highlight functioning parenchyma. Cysts appear as black holes interspersed on a blanket of bright parenchyma. The renal pelvis contains highly concentrated gadolinium. As the disease progresses, the cysts become more numerous; the largest cysts in each kidney are the oldest. In the late stage, there is sufficient functioning parenchyma to maintain a normal GFR despite massive distortion. On the T₂-weighted images (bottom row), the cysts are bright. Cysts as small as 3 mm in diameter can be detected. Panel B shows an ultrasound scan from a patient with an advanced case of autosomal dominant polycystic kidney disease. Cysts are identified by the dark areas. The axial CT scan in Panel C, from a patient with a slightly decreased GFR (stage 2 chronic kidney disease), shows functioning parenchyma enhanced by intravenously administered contrast material. Concentrated contrast material can be seen in patches between cysts and in the renal pelvis.

Figure 3. Relation between Age and Total Kidney Volume in Patients with Autosomal Dominant Polycystic Kidney Disease

Total kidney volume (the sum of the volumes of the left and right kidneys) is shown in 232 women (blue data points) and men (red data points) studied over a 3-year period. The total kidney volume increased progressively in most patients but at widely differing rates. The two black lines superimposed on the data points demarcate slow, moderate, and rapid rates of progression. The rate of disease progression in individual adults at any age can be determined by measuring kidney length, width, and thickness on MRI, CT, or ultrasound scans and estimating the kidney volume with the ellipsoid equation.