Renal Failure from Bladder Acontractility in Untreated X-Linked Nephrogenic Diabetes Insipidus
- Genetic Diseases: Tubulopathies
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
- Syed, Dureya, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Sedlacek, Martin, Icahn School of Medicine at Mount Sinai, New York, New York, United States
A lot is known about about the genetics and molecular pathophysiology of hereditary nephrogenic diabetes insipidus (DI) but there is little information on the long term renal outcome of this condition. Case series show that nephrogenic DI can lead to CKD but the mechanism is unclear. Here we report a patient with untreated x-linked nephrogenic DI who developed renal failure from bladder acontractility.
A 45 year old man presented to the emergency room with a distended abdomen and 10lbs weight gain over several weeks. Ultrasound showed a large bladder and bilateral severe hydronephrosis. His serum creatinine was 1.36mg/dl, increased from a 1.2mg/dl previously. Bladder catheterization produced immediate drainage of 7.5L of urine. In the following hours large urine output was noted. The next morning the patient’s serum creatinine was 1.5mg/dl, serum sodium 149mEq/L and serum osmolality 307mOsm/L. The urine osmolality was 84mOsm/L, sodium <20 and specific gravity 1.003. An ADH level was elevated at 16.3pg/ml. The patient was diagnosed with nephrogenic DI at birth and lost to follow up since his early teenage years. He has three brothers with DI and an adult son who is not affected. X-linked nephrogenic DI was confirmed by genetic testing showing substitution of guanosine by adenosine at codon 296 of the AVP Receptor 2 gene, introducing an early stop codon. Imaging showed a normal sized prostate, cystoureteroscopy was normal except large bladder capacity and urodynamic studies revealed detrusor acontractility. The patient received fluids and was discharged on HCTZ and with an indwelling Foley catheter. He learned to self-catheterize and four months later his serum creatinine was 1.02mg/dl and his urine output 7 L per day.
Patients with nephrogenic DI produce urine volumes in the range of 10-12 L and with a bladder volume of 400ml, they will have to urinate at least 25 times in 24 hours, night and day. Because of Poiseuille’s law, increased urine flow leads to increased pressure, causing hydronephrosis and bladder distention which in turn leads to detrusor dysfunction and ultimately bladder acontractility. We suspect this chain of events is a frequent cause of renal failure in DI, preventable by flow reduction via diuretic treatment and reduced osmole diet. Straight catheterization can improve renal function in patients with bladder acontractility.