In addition to space concerns, recurrent urinary tract infections, chronic pain, renal cell carcinoma, chronic hematuria, or chronic cyst infections can necessitate a nephrectomy.43,44 A laparoscopic approach with decompression of cysts or removal of only one kidney is preferred.43,45 If removal of both kidneys is required before a transplant, the patient must be maintained on dialysis until after transplantation. Since the transplant waiting list can exceed seven years in some areas, most patients arrange for a willing live donor before agreeing to a bilateral nephrectomy.46,47
Dialysis
Either peritoneal dialysis (PD) or hemodialysis (HD) can be offered to patients with severe ADPKD. Depending on the size of the native kidneys and the history of previous abdominal surgery, PD often offers a better chance of survival in these patients, particularly compared with patients who have ESRD associated with other causes.48
For management of the patient with ADPKD who receives PD, it can be difficult to differentiate between the pain of a cyst and the pain of a peritoneal infection. Generally, cyst rupture is accompanied by hematuria; and peritonitis, by cloudy fluid.5 Management provided by an experienced nephrologist and PD nurse is vital.
In ADPKD patients who undergo HD, too, survival is better than in patients who have ESRD with other causes49,50; five-year survival can be as high as 10% to 15%.51 This is likely due to the lower incidence of coronary artery disease in the ADPKD population, compared with patients who have ESRD associated with other chronic diseases.49
FUTURE TRENDS AND ONGOING TRIALS
HALT PKD29,30 is an NIH-funded, double-blind study to determine whether adding an angiotensin receptor blocker (ARB) to standard ACE inhibitor therapy results in a more significant decrease in the progression of renal cysts. The rationale for this is that the ARB is expected to block the renin-angiotensin-aldosterone system in the kidney. Use of ACE inhibitor monotherapy versus ARB/ACE inhibitor therapy is being compared in two study arms: patients between ages 15 and 49 with a GFR of 60 mL/min or greater; and patients between ages 18 and 64 with a GFR of 25 to 60 mL/min.29 To date, preliminary results indicate no benefit in adding the second medication.49
The TEMPO Trial52 is a multicenter, double-blind study looking at the effect of tolvaptan on renal cyst growth. Tolvaptan is a potent vasopressin receptor antagonist, and in vitro evidence has shown that intracellular cyclic adenosine monophosphate (cAMP) plays a large role in the development of cysts in patients with ADPKD. If it is possible to block the cAMP that is causing cyst growth, progression of ADPKD should slow.53,54 Only short-term effects of tolvaptan use are currently known.55
High Water Intake to Slow Progression of Polycystic Kidney Disease56 is an open-label, nonrandomized trial in which patients drink a minimum of
3 L of water. Previously, a small study showed that an increase in fluid intake partially suppresses the urine osmolality and the serum antidiuretic hormone (ADH) levels.57 According to this theory, increasing water intake to greater than 3 L/d may result in complete suppression of ADH and cAMP. This is a small study (n = 20),56 since patients with ADPKD are likely to have urinary concentrating defects, and hyponatremia is a concern is in these patients.58
Sirolimus and ADPKD59 is an open-label randomized study to see whether sirolimus (also known as rapamycin) can reduce cyst growth. Originally, it was noted that posttransplant ADPKD patients underwent a regression of both liver and kidney cysts when they were taking sirolimus, and a preliminary crossover study was done.60 However, preliminary results at 18 months showed no difference in renal growth or cyst growth but did show kidney damage as determined by an increase of proteinuria in the treatment group.59 The study is still in progress.
Somatostatin in Polycystic Kidney61 is a long-term (three-year) study following patients who agreed to participate in a randomized, double-blind protocol; in it, an intramuscular injection of either an octreotide (ie, somatastatin) or placebo was administered every four weeks for one year in an effort to reduce the size of kidney and liver cysts.62 At one year, the quality of life in the treatment group was rated better, as measured by pain reduction and improved physical activity. Cyst growth in the treatment group was smaller for both the kidney and liver. However, the GFR decreased to the same degree in both groups.62
CONCLUSION
ADPKD is a common, often overlooked genetic disease that is a cause of hypertension. ADPKD’s presenting symptoms of flank pain, back pain, and/or hematuria often bring the patient to the provider, but a high index of suspicion must be maintained to diagnose these patients at an early age. Due to the variable presentation even within affected families, many patients do not realize that their family carries the PKD gene.