Approach Considerations
In patients with autosomal dominant polycystic kidney disease (ADPKD), pharmacologic therapy is necessary to accomplish the following:
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Control blood pressure; rigorous blood pressure control is recommended in early ADPKD [38]
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Control abnormalities related to kidney failure
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Treat urinary tract infections
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Treat hematuria
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Reduce abdominal pain produced by enlarged kidneys
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Slow kidney function decline
Patients with ADPKD who progress to end-stage renal disease may require hemodialysis, peritoneal dialysis, or kidney transplantation. For more information, see Chronic Kidney Disease and Kidney Transplantation.
In patients with heart murmurs, institute routine American Heart Association antibiotic prophylaxis.
Metabolic problems related to kidney failure that need to be controlled include the following:
Management of intracranial aneurysms is influenced by their size and location; monitoring is usually sufficient for aneurysms that are less than 7 mm in diameter and are located in the anterior circulation, as these are less likely to rupture. [34] Rozenfeld and colleagues reported that patients with ADPKD who undergo treatment for intracranial aneurysms are especially likely to experience complications: compared with controls, patients with ADPKD experienced higher rates of iatrogenic hemorrhage or infarction, embolic infarction, and carotid artery dissection after endovascular coiling, and higher rates of iatrogenic hemorrhage or infarction after surgical clipping. [39]
Tolvaptan
Tolvaptan (Jynarque), a selective vasopressin V2-receptor antagonist, is approved in the United States and Europe for slowing kidney function decline in adults at risk of rapidly progressive ADPKD. [40, 41] Approval in the US was based on two phase 3 clinical trials.
Treatment with tolvaptan led to improvement in glomerular filtration rate (GFR) during the 1-year REPRISE (Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD) trial. The change from baseline in the estimated GFR (eGFR) was -2.34 mL/minute per 1.73 m2 in the tolvaptan group compared with -3.61 mL/min/1.73 m2 in the placebo group (P< 0.001). [42] In the extension trial (TEMPO 3:4) eGFR differences produced by the third year of the trial were maintained over the next 2 years of tolvaptan treatment.
The primary endpoint in the TEMPO 3:4 and TEMPO 4:4 studies was the intergroup difference for rate of change of total kidney volume (TKV). The trial met its prespecified primary endpoint of 3-year change in TKV (P< 0.0001). The difference in TKV between treatment groups mostly developed within the first year, the earliest assessment, with little further difference in years 2 and 3. In years 4 and 5 during the TEMPO 3:4 extension trial, both groups received tolvaptan and the difference between the groups in TKV was not maintained. [43, 44]
Investigative Therapies
The two-year phase II TAME-PKD study, conducted in 97 patients with early-stage ADPKD, found that long-term use of metformin is safe and tolerable. However, while metformin reduced the decline in estimated glomerular filtration rate (eGFR) compared with placebo (-1.71 versus -3.07 mL/min/1.73 m2 per year, respectively), the difference was not statistically significant. [45] A major phase III trial of metformin in ADPKD is scheduled. [46]
A meta-analysis of 10 randomized controlled trials evaluating somatostatin analogs (eg, octreotide, lanreotide) as therapy for polycystic kidney disease or polycystic liver disease concluded that the use of somatostatin analogs slows increases in total liver volume (TLV) and lower total kidney volume (TKV) but does not affect eGFR. [47]
Salsalate, a prodrug dimer of salicylate, improved kidney survival and reduced cystic kidney disease severity in a mouse model. [48]
Diet and activity
Although a low-salt diet is recommended when hypertension or kidney failure is present, no other special diet reportedly is of benefit.
Patients should avoid contact sports in which direct trauma to the back or abdomen is likely. This is especially important with larger, palpable kidneys in order to minimize the risk of rupture.
Blood Pressure Control
In patients with kidney disease and moderately increased albuminuria, the goal is a blood pressure of 130/80 mm Hg or less. [49] If more than 1 g/day of urinary protein is present, the target blood pressure is less than 125/75 mm Hg. Achieving good blood pressure control helps slow the progression of kidney disease. [50] A study by Patch et al showed that when intensity and coverage of antihypertensive therapy were increased, mortality decreased for patients with ADPKD. [51]
The drugs of choice for this condition are angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril, lisinopril) or angiotensin II receptor blockers (ARBs) such as telmisartan, losartan, irbesartan, and candesartan. These agents remain the most recommended drugs to treat hypertension in patients with ADPKD, although studies of the renin-angiotensin-aldosterone system have not convincingly demonstrated that it plays an important role in its pathogenesis. [52] Calcium channel blockers are not recommended.
In patients with advanced kidney disease, ACE inhibitors and ARBs can exacerbate kidney failure or increase serum potassium levels. Therefore, these patients require regular monitoring of serum chemistry values.
Infectious and Other Disorders
Urinary tract infections (UTIs) occur in 30-50% of ADPKD patients and most frequently in women. Gram-negative bacteria are the most common pathogens.
Distinguishing between infections of the bladder, renal parenchyma, and cysts is important because the treatment for each condition is different. Treating infected cysts requires antibiotics that penetrate into the cyst. Useful agents are ciprofloxacin, trimethoprim-sulfamethoxazole, clindamycin, and chloramphenicol.
Hematuria
Hematuria is frequent in patients with ADPKD. It usually results from cyst rupture or stone passage. Instruct the patient to drink large amounts of water, to rest, and to take a pain killer if necessary. Hematuria is usually self-limited. Hospitalization is necessary if the patient is still bleeding after several days or if the amount of blood is substantial.
Abdominal pain from enlarged kidneys
Avoid nonsteroidal anti-inflammatory drugs (NSAIDs), because they can worsen renal function and potentiate hyperkalemia. Treatment involves surgical cyst decompression, which is effective for pain relief in 60-80% of patients. See Surgical Drainage, below.
Surgical Drainage
If infected renal or hepatic cysts do not respond to conventional antibiotic therapy, surgical drainage may be necessary. This procedure is usually performed with ultrasonographically guided puncture. [53]
Cysts may become large enough to cause abdominal discomfort or pain. Typically, acute pain is from cyst hemorrhage or an obstruction by a clot, stone, or infection. [54] When one or more cysts can be identified as causing the pain, the symptoms can often be abated by open- or fiberoptic–guided surgery to excise the outer walls and to drain them.
Approximately 25% of patients with the most severe pain do not gain relief from surgery or pharmacologic therapy with narcotics. These individuals usually have inaccessible cysts in the medullary portions of the kidneys. Nephrectomy is used as a last resort to control the pain in these patients. Nephrectomy is often necessary when there is not enough room for a kidney graft.
Severe polycystic liver disease can result in massive hepatomegaly (see image below). When the liver becomes so large that it prevents the patient from obtaining normal nutrition or causes severe abdominal discomfort, a surgical procedure is necessary. Surgical intervention may range from unroofing several cysts to a partial hepatectomy.
Partial hepatectomy is difficult because of the characteristics of the polycystic liver. Only very expert surgeons should proceed with this surgical procedure.
When the polycystic liver causes portal hypertension or is very large with nonresectable areas, liver transplantation may be necessary.
Special attention should be paid when bilateral nephrectomy has to be carried out in patients with severe liver involvement. Several cases of refractory ascites after bilateral nephrectomy have been reported in these patients.
Consultations and Long-Term Monitoring
Consultations may be indicated under the following circumstances:
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Nephrologist upon evidence of renal insufficiency, hypertension, microalbuminuria, or concentrating defect
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Invasive radiologist for cyst sclerosis or drainage
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General surgeon for nephrectomy, cyst decompression, unroofing, or surgical hepatic procedures
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Neurosurgeon for intracranial aneurysms
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Cardiologist for valvular abnormalities
Ensure that a patient with ADPKD who is nonhypertensive and has normal renal function undergoes blood testing and ultrasonography of the kidneys every 1-2 years. Schedule more frequent follow-up studies for patients with high blood pressure. Hypertension is common, occurring in as many as 50-70% of patients before the onset of renal failure. Patients with renal failure require more frequent monitoring, based on the severity of their condition.
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Polycystic kidney.
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Polycystic kidney disease and massive polycystic liver disease.
