Adult polycystic kidney disease management
Cysts (yellow) have replacd the majority of kidney tissue in this patient with PKD.
Extrarenal findings may include hepatic and pancreatic cysts. If the results of the ultrasound are inconclusive, CT or MRI may be beneficial, as these imaging studies are more sensitive than ultrasound for detecting cysts. MRI may also be used to diagnose intracranial aneurysms if patients have headaches or a family history of stroke. Optional procedures include barium enema to diagnose diverticuli and an echocardiography to evaluate for valvular abnormalities.10,11
Genetic testing can be with a 95% accuracy of diagnosis: (1) when imaging results are equivocal or inconclusive; (2) to confirm a presumed diagnosis in the absence of family history of ADPKD (conclusive diagnosis in these patients relies on mutation analysis); and (3) when a definite diagnosis is required in a younger patient (e.g., a potential living related kidney donor).11
Treatment options
No proven treatment available will prevent or delay the progression of ADPKD. Treatment options are mostly supportive and preventive with the goal of slowing the progression of renal failure, managing complications, and prolonging life.11 Some promising trials are under way for new medications that may slow the rate of cyst formation, but the results will not be known for several years.
The targeted complications to be considered include:
Lifestyle changes. Diet modification should include protein restriction, lowered salt intake, decreased caffeine intake, and increased daily water intake. One study in progress is designed to determine the effects of increased water intake in amounts greater than three liters per day.12 The increased water intake is suspected to suppress vasopressin, which is thought to play a role in cyst formation. Patients who consume such large volumes of water are at heightened risk for hyponatremia, so sodium levels should be monitored regularly.10,13
Hypertension. Tight control of BP is thought to delay or prevent progression of the disease. Increased BP is considered attributable to an activation of the RAAS, so blockage of this system is the focus of treatment. Although no guidelines have been set for ADPKD, most clinicians agree to follow the recommendation from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure of a BP <130/90 mm Hg. Studies are under way to determine whether even lower BP levels are beneficial. ACE inhibitors are considered first-line treatment followed by angiotensin II receptor blockers (ARBs) and direct renin inhibitors. Patients taking ACE inhibitors must have their creatinine and potassium monitored routinely for increased levels. Alternate treatment options include calcium channel blockers, beta blockers, and/or diuretics.8,11,13
UTIs. Increased frequency of UTIs is correlated with poorer outcomes in patients with PKD. Patient education and prompt treatment is crucial. Complications of UTI include obstruction and migration of infection to include the kidney, which can be devastating. Treatment can be started empirically with an antibiotic, but a specimen should be sent for culture and sensitivity so that proper therapy can be provided.8,11,13
Hyperlipidemia. Because elevated lipid levels have a coronary heart disease risk equivalent in patients with PKD, aggressive treatment should be implemented as needed. Statins are the first treatment option for lowering LDL and raising HDL. Statins may help preserve renal function, but this has not been proven.8,11,13
Pain. Pain can be caused by compression associated with enlarged kidneys, renal infections, cyst rupture, kidney stones, and even renal tumors. Most sources are self-limiting and can be controlled with rest and either acetaminophen, nonsteroidal anti-inflammatory drugs, or opioid analgesics. Treatment options for enlarged cysts include aspiration, sclerotic injections, or laparoscopic/surgical cyst fenestration.8,11,13
Nephrolithiasis. There are several ways to manage renal stones. For small stones, pain management with conservative observation may be indicated. Potassium citrate is indicated for three types of stones seen in ADPKD: (1) uric acid stones; (2) hypocitraturic calcium oxalate nephrolithiasis; and (3) distal acidification defects.11 For stones that do not spontaneously pass, urology referral is indicated. At this point, lithotripsy, percutaneous nephrolithotomy, and retrograde retrieval of stones are viable treatment options.8,11,13
Extrarenal complications. Intracranial aneurysms should be managed by a neurologist. Clipping or coiling are options for aneurysms >8 mm. Monitor heart-valve disorders with echocardiography, which can be used to assess the severity of need for valve-replacement surgery.8,11,13
Renal failure. A patient progressing into Stage 4 of renal failure should prepare for kidney replacement. Renal transplant is the treatment of choice. Look within the family for possible donors, and place the patient on the donor waiting list. Dialysis is a second-line option for a patient on the donor waiting list or a candidate suitable for replacement. Access for dialysis may be through a vascular site, including a catheter, graft, or fistula. Another viable option is peritoneal dialysis.8,11,13
Medications under trial. Several trials are examining treatments for ADPKD. The more promising include the vasopressin receptor antagonist tolvaptan, the somatostatin inhibitor octreotide, the kinase inhibitor everolimus, epidermal growth factor receptor inhibitors, tyrosine kinase, Src kinase, roscovitine, and ACE inhibitor/ARB antagonist combinations.8,11,13 For more information of ongoing clinical trials, visit ClinicalTrials.gov.
Prognosis
Approximately 50% of ADPKD patients will develop ESRD and require either a renal transplant or dialysis by age 60 years. The major factor for prognosis is the form of gene mutation present in the patient. Although the two forms of ADPKD (ADPKD1 and 2) share similar clinical features, renal prognosis is vastly different. Studies show that ADPKD2 is a milder disease, based on the age of onset of ESRD. The median age of renal survival for those with this form of ADPKD is 68 years. For those with ADPKD1, the median age of renal survival is 53 years.6
Other factors that can improve outcomes are tight control of BP, adherence to dietary recommendations, and prevention/prompt treatment of UTIs.5,6
Conclusion
The understanding of ADPKD has improved over the past decade. A comprehensive approach to caring for people with this disease that includes early detection, management of symptoms, and referral to a nephrologist when appropriate is imperative.
Mr. Moon is a second-year student in the physician assistant program at the Medical College of Georgia in Augusta, where Dr. Gunder is assistant professor and director of research and faculty development, and Ms. Steele is assistant professor.
References
2. Ross JE. Diseases of the kidney. In: AK David, DM Phillips, JE Scherger, TA Johnson, eds. Family Medicine: Principles and Practice, 6th ed. New York: Springer-Verlag New York, Inc.; 2003:838.
3. Patel V, Chowdhury R, Igarashi P. Advances in the pathogenesis and treatment of polycystic kidney disease. Curr Opin Nephrol Hypertens. 2009;18:99-106.
4. Gunder LM, Martin SA. Essentials of Medical Genetics for Health Professionals. Sudbury, Mass.: Jones & Bartlett Learning; 2011:155.
5. Salant DJ, Patel PS. Polycystic kidney disease and other inherited tubular disorders. In: Kasper DL, Braunwald E, Fauci AS, et al., eds. Harrison's Principles of Internal Medicine. 17th ed. New York, N.Y.: The McGraw-Hill Companies; 2008:1797-1805.
6. Watnick S, Morrison G. Cystic diseases of the kidney. In: McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49th ed. New York, N.Y.: McGraw-Hill; 2010:846-848.
7. Mcaninch JW. Adult polycystic kidney disease. In: Tanagho EA, McAninch JW, eds. Smith's GeneralUrology. 17th ed. Columbus, Ohio: McGraw-Hill;2008:507-512.
9. Ravine D, Gibson RN, Walker RG, et al. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet. 1994;343:824-827.
10. eMedicine. Polycystic kidney disease.
11. Epocrates Online. Polycystic kidney disease.
13. UpToDate. Course and treatment of autosomal dominant polycystic kidney disease.
All electronic documents accessed May 15, 2011.
