Abstract: PO1281
Management of a Patient with ADPKD Who Needs Lithium
Session Information
- Cystic Kidney Disease - II
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Senter, Katharine I., Thomas Jefferson University Sidney Kimmel Medical College, Philadelphia, Pennsylvania, United States
- Maarouf, Omar H., Thomas Jefferson University Sidney Kimmel Medical College, Philadelphia, Pennsylvania, United States
- Zhang, JingJing, Thomas Jefferson University Sidney Kimmel Medical College, Philadelphia, Pennsylvania, United States
Introduction
N/A
Case Description
A 35-year-old female with borderline personality disorder and schizoaffective disorder presented to nephrology for autosomal dominant polycystic kidney disease (ADPKD). Her biological father had ADPKD and was on dialysis at the time of death. The patient has taken lithium for 10 years, and only lithium allows her to work and live independently. She presented with polydipsia and polyuria, indicating possible nephrogenic diabetes insipidus (DI) from lithium, essential hypertension since age 30, and constant headache; brain MRI was negative for aneurysm.
Labs showed a lithium level between 0.3-0.9 mmol/L, creatinine between 0.6-0.75 mg/dL, eGFR of 85-90 ml/min, urine protein:creatinine ratio of 0.27-0.32 g/g, and urine osmolality <100 mOsmol/kg. She has been treated with 2.5 mg lisinopril,10 mg amiloride, and 1350 mg lithium daily. Abdominal MRI without contrast showed scattered liver cysts and innumerable bilateral kidney cysts. Kidney volume indicated Mayo Class 1C PKD. Her father developed ESRD in his late 50s, suggesting rapidly progressive ADPKD class.
Lithium nephropathy is usually characterized by 1-2 mm renal microcysts (Khan et al, Int J Psychiatr Med 50(3):290-298). The patient’s larger cysts, total kidney volume, and liver cysts suggest ADPKD. Genetic testing showed that the patient has a heterozygous mutation in c.12445-1G>T, expected to cause altered splicing and function of the PKD1 gene.
Discussion
Finding an appropriate agent to slow CKD progression is the current strategy to manage PKD. Her condition is complicated by likely lithium nephropathy. The TEMPO trial (Torres et al, N Engl J Med 367:2407–2418, 2012) showed that tolvaptan helps slow rapidly progressive ADPKD by inhibiting vasopressin’s effect, reducing cAMP production, further inhibiting cyst formation and growth (Wang X et al, J Am Soc Nephrol 19: 102–108, 2008; Aihara M et al, J Pharmacol Exp Ther 349: 258–267, 2014). Lithium can also inhibit vasopressin in the kidney, leading to nephrogenic DI (Bokenhauer et al, Nat Rev Nephrol11(10):576-88, 2015). In ADPKD, tolvaptan helps achieve a urine osmolality of less than 300 mOsmol/kg (Torres, Clin J Am Soc Nephrol. 13(11):1765-1776, 2018). Our patient already has polyuria and urine osmolality below 100 mOsmol/kg. Her condition requires agents targeting other pathways. For now, she is on lisinopril, with BP <110/75, and amiloride to limit polyuria.