The patient wanted to know what lifestyle modifications she should make and what therapies are available to her.
A 24-year-old woman came to a renal clinic for evaluation of autosomal dominant polycystic kidney disease (ADPKD). Her mother has ADPKD and is currently on dialysis. One of her sisters also has ADPKD. She recently went to the local health fair where she was found to have kidney cysts by ultrasound. A subsequent formal kidney ultrasound showed numerous cysts in both kidneys. The right kidney measured 15.1 cm in length and the left kidney measured 14.8 cm in length. Both demonstrated increased echogenicity. Her serum creatinine was 0.6, with an estimated glomerular filtrate rate (eGFR) of 128 mL/min/1.73m2 per the CKD-EPI creatinine equation. She had no proteinuria or hematuria. Her blood pressure was 120/65 mm Hg and 113/66 mm Hg during 2 clinic visits. There is no family or personal history of stroke or cerebral aneurysm. She wanted to know what lifestyle modifications she should make and what therapies are available to her. She also wanted to know the impact of this diagnosis on her plans to have a family in the future.
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This case was prepared by Yongen Chang, MD, PhD, Assistant Clinical Professor, Division of Nephrology and Hypertension, University of California Irvine.
1. Chapman AB, Devuyst O, Eckardt KU, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2015;88:17-27. doi:10.1038/ki.2015.59.
2. Grantham J J, Torres VE, Chapman AB, et al. Volume progression in polycystic kidney disease. N Engl J Med 2006;354:2122-2130. doi:10.1056/NEJMoa054341.
3. Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. New Engl J Med 2012;367: 2407-2418. doi:10.1056/NEJMoa1205511.
4. Perico N, Antiga L, Caroli A, et al. Sirolimus therapy to halt the progression of ADPKD. J Am Soc Nephrol 2010;21:1031-1040. doi:10.1681/ASN.2009121302 (2010).
5. Walz G, Budde K, Mannaa M, et al. Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2010;363:830-840. doi:10.1056/NEJMoa1003491.
ADPKD is characterized by cyst formation in multiple organs including the kidney (and the liver) leading to chronic kidney disease (CKD). A majority of patients carry mutations in PKD1 or PKD2 gene. Since it is an autosomal dominant disease, one copy of the mutant gene is sufficient to cause disease. Offspring of ADPKD patients have a 50% chance of inheriting the gene and, therefore, develop the disease. With the advancement of in vitro fertilization technology, embryos can be screened for PKD gene mutations. ADPKD women with normal blood pressure and kidney function have favorable course of pregnancy. However, their risk of developing hypertension and preeclampsia during pregnancy is higher1. Exposure to estrogen and progesterone during pregnancy could also potentially aggravate polycystic liver disease1.
Medical management of ADPKD includes treating hypertension, standard CKD care, screening for cerebral aneurysm if there is positive family history. A significant proportion of patients (50%) reaches end stage renal disease (ESRD). The decline in glomerular filtrate rate (GFR) is associated with higher rate of cyst growth and increased total kidney volume (TKV)2. Hypertension is prevalent in this population secondary to activation of renin-angiotensin-aldosterone system (RAS). Thus, agents to suppress RAS system such as ACEI or ARB are recommended as first line agents for ADPKD patients with hypertension. The blood pressure goal for ADPKD patients is similar to that for patients with CKD (less than 140/90 mm Hg) since there is lack of evidence to support a lower blood pressure goal1. Since this patient has normal blood pressure and has no proteinuria. There is no strong indication to start ACEI or ARB at this time. Various studies showed pathologic role of the antidiuretic hormone arginine vasopressin in ADPKD. Therefore, patients are advised to increase their water intake to suppress arginine vasopressin activity although its long term efficacy is not known1. Due to a potential effect on intracellular cAMP activity, it is recommended that patients limit caffeine intake1.
New therapies for ADPKD are emerging. A large-scale randomized control trial showed that the arginine vasopressin V2 receptor antagonist tolvaptan slowed down the growth rate of TKV and decline in eGFR for those with TKV over 750 mL3. This led to approval of tolvaptan use for ADPKD in Japan. The US FDA approval is pending review of additional data. This patient’s kidney length is 15cm, which likely represents TKV less than 750 ml. However, further imaging such as MRI is needed to better assess her TKV before we start tolvaptan. Two small trials also examined the effects of mTOR inhibitors (everolimus and sirolimus) in ADPKD patients with early CKD. Both demonstrated the ability to reduce growth rate of TKV but did not halt CKD progression 4,5.