Relevance of ultrasound examination in general practice. A case report of a patient with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease is a genetic disorder which results in the development of multiple cysts in the kidneys and other parenchymal organs. The two genes in which mutations are known to cause autosomal dominant polycystic kidney disease are PKD1 and PKD2. Approximately 50% of individuals with autosomal dominant polycystic kidney disease will develop end-stage renal disease by the age of 60. Early stages of the disease are usually asymptomatic and at the moment of establishing a definitive diagnosis, complications and associated disorders, including end-stage renal disease, occur frequently. About 95% of individuals with autosomal dominant polycystic kidney disease have an affected parent and about 5% have a de novo mutation. Each child of an affected individual has a 50% chance of inheriting the mutation. The first symptoms of disease usually develop in the third or fourth decades of life. Imaging examinations of relatives at risk allow for an early detection when no clinical symptoms are present as well as enable treatment of complications and associated disorders. Ultrasound examination as a basic and minimally invasive imaging technique can be easily used in general practice. In the majority of patients with autosomal dominant polycystic kidney disease, sonography allows for a certain and reliable diagnosis of this disease. Additionally, it enables to perform follow-up examinations both of the patient and their family. The possibility of ultrasound imaging in general practice broadens clinical examination and facilitates establishing a proper diagnosis. The paper presents a case report of a patient with autosomal dominant polycystic kidney disease. Its aim was to present the relevance of ultrasound examination in general practice.

Introduction

The need for having and consequently, the ability to operate ultrasound (US) equipment in the practice of a family doctor is still a significant and unregulated issue. Since possessing US equipment is not a prerequisite for running medical practice as part of primary care, many physicians must refer to other specialists, which prolongs diagnosis. Moreover, the lack of direct contact between specialists may lead to diagnostic uncertainties and wrong direction of US examination. Therefore, it appears justifiable to provide ultrasound education to possibly the greatest number of practitioners in order to diagnose abdominal diseases early – in the office of a general practitioner (GP).

Case report

A 48-year-old female patient reported to the GP with bilateral lumbar pain and concomitant hematuria. After the interview and physical examination, the patient was scanned by means of ultrasound which revealed multiple cysts of various sizes, considerable enlargement of both kidneys and coexisting liver cysts.

The patient underwent other laboratory tests which demonstrated elevated serum creatinine (6.67 mg/dl) and considerably decreased eGFR (12.2 ml/min). The patient was referred to the nephrological ward where she was qualified to renal replacement therapy (vascular dialysis). The family doctor also examined the patient's children (a daughter and two sons), so far healthy. In all three cases, ultrasound examination confirmed the diagnosis of autosomal dominant polycystic kidney disease (ADPKD). All the children manifested numerous renal cysts but the size of the kidneys was normal. The patients were referred to genetic and nephrological clinic.

Right kidney with multiple cysts – longitudinal view

Right kidney, enlarged to 23.38 cm with multiple cysts – longitudinal view

Left kidney, enlarged to 19.05 cm with multiple cysts – longitudinal view

Cysts in the hepatic parenchyma of the presented patient

Right kidney of the patient's son with multiple cysts – longitudinal view

Right kidney of the patient's son in longitudinal view – power Doppler ultrasound

Right kidney of the patient's son in longitudinal view – bi-flow imaging

Discussion

ADPKD is a genetic disorder resulting in the development of multiple cysts in the renal cortex and medulla(. The disease usually manifests itself in the third or fourth decades of life. It is the most frequent genetically-determined kidney disease and constitutes the fourth most common cause for renal replacement therapy. Moreover, following hypercholesterolemia and dominant osteosclerosis, ADPKD is the third most common disorder associated with single gene mutation. The mutation concerns polycystin 1 gene on chromosome 16 (in 85%) and, more rarely, polycystin 2 gene on chromosome 4(. The disease is characterized by various expression but it is fully penetrant. Its incidence is greater than that of Huntington's disease, hemophilia, sickle-cell anemia, cystic fibrosis, muscular dystrophy and Down syndrome altogether. Its incidence constitutes 1:400–1:1000 live births(.

The diagnosis of ADPKD is based on imaging examinations where multiple cysts in both kidneys and enlargement of the kidneys constitute a typical presentation. Ultrasound examination is the primary test with high sensitivity and specificity. During ultrasound diagnosis, Ravine's criteria, presented in tab. 1, are taken into account. If doubts occur, usually computed tomography is conducted.

Tab. 1

Ravine's criteria(

Age	Number of cysts
	Positive family interview	Negative family interview
< 30 years	At least 2 in one or two kidneys	At least 5
30–60 years	At least 2 in each kidney	At least 5
> 60 years	At least 4 in each kidney	At least 8

The first symptoms of ADPKD usually occur in the third or fourth decades of life, but thanks to imaging examinations the disease may be diagnosed earlier. Family interview is significant – the risk of developing the disease in children and siblings of the patient is 50% (autosomal dominant inheritance pattern). Therefore, imaging examinations should also be carried out in the relatives of ADPKD patients. In the case of de novo mutation, the individual does not inherit but passes the disease(. In the office of a GP, it is easier to invite the patient's relatives for examination and if the disease is detected in its asymptomatic stage, it is possible to conduct conscious follow-up examinations and counteract the complications.

One of the symptoms of ADPKD is chronic pain localized in the lumbar region, which is caused by the enlargement of the kidneys. Many patients with ADPKD have arterial hypertension and 20–30% of them manifest it in childhood. Additionally, macro- or microscopic hematuria is frequently observed and the impaired ability to condense urine by the kidneys causes nycturia(. In approximately 20% of these patients, ultrasound examination also reveals nephrolithiasis. Moreover, infections of the urinary system result from infection of the renal parenchyma or urinary bladder and may also develop secondary to infection of the cysts or their hemorrhagic lesions. Such complications may constitute an indication for active ADPKD treatment. On ultrasound, an infected cyst shows slight scattered echoes of its morphologically rich fluid. In hemorrhagic cysts, on the other hand, one may detect solid masses of clots with low echogenicity, bands of fibrin and anechoic fluid areas. If there are doubts connected with the differentiation from a proliferative process, the diagnosis should be expanded(.

What is more, significant symptoms of ADPKD, which are not directly associated with the kidneys, are cysts in the liver, spleen, pancreas and ovaries as well as colonic diverticulosis. The course of the disease may be negatively affected by intracranial aneurysms which may lead to permanent neurological damage and even to death as a result of subarachnoid hemorrhage. Other symptoms, which are not directly related to the kidneys, are defects of the mitral, aortic and tricuspid valves(.

At present, the causative therapy of the disease does not exist. It is merely possible to slow its development and minimize clinical symptoms. Early treatment of its complications, mainly arterial hypertension, is of fundamental importance. The first-choice medicines are ACE inhibitors and sartans. This therapy requires monitoring the kidney function and electrolytes. Urinary tract infections, however, are treated in accordance with current standards and when a cyst with purulent contents is suspected, antibiotics penetrating into the cyst are administered. If renal failure develops in a patient, renal replacement therapy or, the most optimally – kidney transplantation, become essential. Another problem may be posed by nephrolithiasis which frequently requires surgical treatment. Similarly, surgical intervention is essential if compression on the pelvicalyceal system develops and when urine outflow is inhibited. Currently, the influence of ACE inhibitors on the course of ADPKD and on the decrease of glomerular filtration rate is being studied in clinical trials. Vasopressin receptor V2 antagonists (vaptans), immunosuppressant drugs (sirolimus and everolimus) and octreotide were thought to be very promising. However, clinical trials revealed their average influence on the course of the disease and significant adverse reactions.

Conclusions

In the presented case, ultrasound examination enabled fast and accurate diagnosis of the patient and her family. This allowed for the detection of an asymptomatic disease. In such a situation, it is possible to monitor the course of the disease and implement proper management early. US imaging is a valuable supplementation of a physical examination and in certain cases, it should constitute its integral part.