Polycystic Kidney Disease Treatment & Management

The aim of current treatment for ADPKD is to slow the decline in kidney function and reduce extrarenal complications. Specific disease features to address include the following ^[32]  :

• Hypertension; rigorous blood pressure control is recommended in early ADPKD ^{[3, 25]}
• Abnormalities related to kidney failure
• Urinary tract infections
• Cyst hemorrhage and hematuria
• Abdominal pain caused by enlarged kidneys
• Nephrolithiasis
• Polycystic liver disease
• Intracraneal aneurysms

Patients with ADPKD who progress to advanced chronic kidney disease (CKD) may require hemodialysis, peritoneal dialysis, or kidney transplantation. For more information, see Chronic Kidney Disease and Kidney Transplantation.

Metabolic problems associated with advanced CKD that require control include the following ^[33] :

• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia
• Hyperparathyroidism
• Metabolic acidosis

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. When coiling or clipping is used to treat intracranial aneurysms, patients with ADPKD are at greater risk of complications, compared with other patients. Rozenfeld et al reported that 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. ^{[34, 7, 29]}

Tolvaptan

Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved in the United States, Japan, Canada, Europe, and elsewhere for slowing kidney function decline in adults at risk of rapidly progressive ADPKD. ^[22] Factors used to identify rapidly progressive ADPKD include the following:

• Total kidney volume (TKV)/age and rate of change of TKV
• Estimated glomerular filtration rate (eGFR)/age and rate of decline of eGFR
• Genotype (PRO-PKD score; see Overview/Prognosis)
• Family history

Treatment with tolvaptan led to improvement in eGFR in 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 eGFR was -2.34 mL/min/1.73 m² in the tolvaptan group compared with -3.61 mL/min/1.73 m² in the placebo group (P < 0.001). ^[35] In the TEMPO 3:4 and the extension TEMPO 4:4 trial, eGFR differences produced by the third year of the trial were maintained over the next 2 years of tolvaptan treatment. ^[36]

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 TEMPO 3:4 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. ^{[37, 36]}

Tolvaptan causes elevations in liver enzymes in about 5% of recipients. These elevations reverse on discontinuation of the drug. ^[37]

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 eGFR compared with placebo (-1.71 versus -3.07 mL/min/1.73 m² per year, respectively), the difference was not statistically significant. ^{[38, 39]}

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. ^[40]

Salsalate, a prodrug dimer of salicylate, improved kidney survival and reduced cystic kidney disease severity in a mouse model. ^[41]

Many trials have been completed or are under way to investigate different treatments, including the use of statins, vitamin B3 or niacinamide, antiproliferative drugs, and somatostatin analogues. ^[1]

The target blood pressure is ≤110/75 mm Hg in patients aged 18-50 years who have an eGFR > 60 mL/min. Otherwise, the target is ≤130/85 mm Hg. Achieving good blood pressure control helps slow the progression of kidney disease, and the importance of early detection and treatment of hypertension in ADPKD has been demonstrated in several studies.

The HALT A and HALT B PKD clinical trials studied hypertensive ADPKD patients. ^{[3, 24]} Both studies showed that an angiotensin-converting enzyme inhibitor alone can adequately control hypertension in most patients, justifying its use as first-line treatment for hypertension in this disease. HALT A showed that in young patients with normal kidny functioen, lowering blood pressure to levels below those recommended by hypertension guidelines reduced the rate of increase in kidney volume by 14%, the increase in renal vascular resistance, urine albumin excretion, left ventricular mass index, and the rate of decline in eGFR. ^{[5, 24]}

The drugs of choice for this condition are angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril, lisinopril) or angiotensin II receptor blockers (ARBs) such as telmisartan, losartan, irbesartan, and candesartan. Calcium channel blockers are not recommended.

In patients with advanced chronic 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.

Urinary tract infections (UTIs) occur in 30-50% of ADPKD patients, 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 kidney or liver cysts requires antibiotics that penetrate into the cyst. For cyst infections, useful agents are fluorquinolones and trimethoprim-sulfamethoxazole. Recommended durations of treatment vary; these agents are typically given for around 4-6 weeks in complicated cases. Resolution of fever and at least two negative blood and/or urine cultures can be used to determine efficacy of treatment. ^[5]

Cyst hemorrhage and gross hematuria

Hematuria in patients with ADPKD results from kidney 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 and responds well to conservative management. Hospitalization is necessary if the bleeding is substantial or persists after several days.

Abdominal pain from enlarged kidneys

The initial approach to pain management is conservative. Nonopioid agents are preferred. ^[42] Avoid nonsteroidal anti-inflammatory drugs (NSAIDs), because they can worsen kidney function. As in other chronic pain syndromes, tricyclic antidepressants can be helpful and are generally well tolerated. Narcotic analgesics should be reserved for the treatment of acute episodes.

Treatment for severe, refractory cases may also involve surgical cyst decompression, which is effective for pain relief in 60-80% of patients. See Surgical Drainage, below.

Kidney stones

Treatment of nephrolithiasis in patients with ADPKD is the same as in those without ADPKD: high fluid intake and potassium citrate in uric acid lithiasis, hypocitric calcium oxalate nephrolithiasis, and distal acidification defects. Success can be achieved with extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy ^[5] .

Polycystic liver disease

Most people with polycystic liver disease (PLD) have no symptoms and do not require treatment. Treatment of symptomatic disease includes avoiding estrogens and using H2 blockers or proton pump inhibitors for symptomatic relief. Infected liver cysts require antibiotics for 4-6 weeks. ^{[5, 1]}

Intracranial aneurysms

Asymptomatic patients with aneurysms ≤5.0 mm in diameter diagnosed by screening can be observed and followed initially at yearly intervals. If the size increases, surgery is indicated.The management of aneurysms of 6.0-9.0 mm remains controversial. Surgery is usually indicated for aneurysms > 10.0 mm in diameter, and for those that are causing symptoms or have ruptured. ^[5] Surgical treatment of a ruptured aneurysm involves clipping it at its neck. For more information, see Neurosurgery for Cerebral Aneurysm.

If infected kidney or hepatic cysts do not respond to conventional antibiotic therapy, surgical drainage may be necessary. This procedure is usually performed with ultrasonographically guided puncture. ^[43]

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. ^[44] 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 also often necessary for kidney transplant recipients when there is not enough space for the donor kidney.

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 a 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 may be indicated under the following circumstances ^[5] :

• Nephrologist, for management of kidney insufficiency, hypertension, albuminuria, or concentrating defect
• Invasive radiologist, for cyst sclerosis or drainage
• General surgeon, for nephrectomy, cyst decompression, unroofing, or surgical hepatic procedures
• Neurosurgeon, for intracranial aneurysms
• Cardiologist, for valvular abnormalities

Ensure that a patient with ADPKD who is nonhypertensive and has normal kidney 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 kidney failure. Patients with advanced chronic kidney disease require more frequent monitoring, based on the severity of their condition.

Avoid the use of estrogens and possibly progestogens in individuals with severe polycystic liver disease.

Avoid caffeine in large amounts. ^[45] There is no evidence that low or moderate use of caffeinated beverages accelerates the progression of ADPKD. Avoid a high-salt diet. In a brief pilot study, a low-osmolar diet with adjusted water intake to achieve a urine osmolality of ≤280 mOsm/kg H₂O significantly reduced vasopressin in patients with ADPKD. ^[46]

Patients should avoid contact sports where direct trauma to the back or abdomen is likely. This is particularly important in those with larger, palpable kidneys, to minimize the risk of rupture.