ADPKD

Overview

• Inherited multisystemic disease characterized by multiple cyst formation in both kidneys and other organs.

• Prevalence of approximately 1 : 1000, inherited as an autosomal dominant trait.

• Mutations in the PKD1 gene (chromosome 16) account for 85% of cases, and PKD2 (chromosome 4) for about 15%.

Clinical features

• Vague discomfort, acute loin pain, or renal colic.

• Hypertension, hematuria, urinary tract or cyst infections, renal failure.

• Extrarenal manifestations: hepatic cysts, aneurysms, mitral valve prolapse, etc.

Investigations

• Diagnosis based on family history, clinical findings, and ultrasound examination.

• Ultrasound demonstrates cysts in both kidneys.

• MRI may be used for identification.

• Genetic mutation screening is seldom used in routine clinical practice.

Management

• Blood pressure control with ACE inhibitors or ARBs.

• Treatment of complications like infections and nephrolithiasis.

• Tolvaptan slows kidney volume increase and GFR decline.

• Dialysis and transplantation are common treatments.

• Surgery may be considered to alleviate symptoms.

Prognosis

• ESRD develops in approximately 50% of patients with ADPKD by 60 years of age.

Renal artery stenosis (RAS)

• Renal artery stenosis is the narrowing of one or both renal arteries.

• It is a relatively uncommon disorder, presenting clinically with hypertension (secondary hypertension).

• Estimated to occur in about 2% of unselected patients.

Types

• Atherosclerotic type: Most common (90% of patients), associated with atherosclerosis and prevalent in old men, smokers, and diabetics.

• Fibromuscular dysplasia type (10% of patients): Characterized by hypertrophy of the media (medial fibroplasia), often leading to hypertension in young women.

Pathology

• Renal artery stenosis results in reduced renal perfusion pressure, activating the renin-angiotensin system.

• This leads to increased angiotensin II, causing vasoconstriction and aldosterone production, resulting in sodium retention by the renal tubules.

• Significant reduction of renal blood flow occurs with over 70% narrowing of the artery

Clinical features

• More likely if hypertension is severe, of recent onset, or difficult to control.

• Asymmetrical kidney size, flash pulmonary edema, peripheral vascular disease, renal impairment, deterioration on ACE inhibitors.

Investigations

• CT angiography or MR angiography for diagnosis.

• Biochemical testing may show impaired renal function, elevated plasma renin activity, and hypokalemia.

• Ultrasound may reveal a size discrepancy between the kidneys.

Management

• Atherosclerotic disease: First-line is medical therapy, including intensive lipid lowering, aspirin, smoking cessation, and hypertension and diabetes control.

• Fibromuscular dysplasia: Pharmacologic treatment for hypertension. Intervention with angioplasty, stenting, or surgery for severe cases.

Renal adenocarcinoma

• Most common malignant tumor of the kidney in adults.

• Twice as common in males, peak incidence between 65 and 75 years.

• Arises from renal tubular cells, clear cell carcinomas being the most common subtype (85%).

Clinical features

• 50% asymptomatic, identified incidentally.

• 60% present with hematuria.

• 40% with loin pain.

• 25% with a mass.

• 10% present with a triad of pain, hematuria, and a mass.

• Systemic effects: fever, raised ESR, polycythemia, coagulation disorders, hypercalcemia.

Systemic effects

• Fever, raised ESR, polycythemia, disorders of coagulation, hypercalcemia, and abnormalities of plasma proteins and liver function tests.

• Result from tumor-secreted products like renin, erythropoietin, PTH-related protein (PTHrP), and gonadotrophins.

Investigations

• Ultrasound is the first-choice investigation for differentiation.

• Contrast-enhanced CT for staging.

• Biopsy if the nature of the lesion is uncertain.

Management

• Radical nephrectomy, including the perirenal fascial envelope and ipsilateral para-aortic lymph nodes, is the treatment of choice.

• Surgery may be considered for solitary metastases.

• Recently, tyrosine kinase inhibitors (sunitinib, pazopanib) and mTOR inhibitors (temsirolimus, everolimus) are mainstays of therapy.

Prognosis

• If confined to the kidney, 5-year survival is 75%, dropping to 5% with distant metastases.

Prostate Cancer-Clinical features

• Often asymptomatic or presents with lower urinary tract symptoms.

• Digital rectal examination (DRE) may reveal a nodular and stony-hard prostate.

Investigations

• Serum prostate-specific antigen (PSA) measurement and DRE are crucial for diagnosis.

• Transrectal ultrasound-guided prostate biopsies for confirmation.

• Pelvic MRI for staging and isotope bone scan for suspected distant metastases.

Management

1. Tumor confined to the prostate: Curable by radical prostatectomy, radical radiotherapy, or brachytherapy.

2. Metastatic prostate cancer: Treated by androgen depletion.

• Surgery: Castration (orchidectomy) or

• Drugs: Androgen receptor blockers (bicalutamide, cyproterone acetate), Gonadotrophin-releasing hormone (GnRH) analogues (goserelin).

3. Failure of hormonal therapy:

• Chemotherapy with docetaxel can be effective.

• Radiotherapy for localized bone pain.

• Pain control with analgesia.

Prognosis

• 10-year survival rate of patients with tumors localized to the prostate is 95%.

• If metastases are present, this falls to 10%.