Monday Pharmaceutical Mystery: How Did Getting Healthy and Losing Weight Result in Kidney Failure?

RG is a male patient aged 45 years who has arrived at the pharmacy to pick up his regular maintenance medications: citalopram at 20 mg per day, lisinopril at 40 mg per day, tamsulosin at 0.4 mg per day at bedtime, and esomeprazole at 40 mg per day.

RG is a regular customer of the pharmacy who recently lost 45 pounds in 3 months as a result of a whole foods diet and avoiding sugar and alcohol. As the pharmacist rang him up at the cash register, they congratulated him on the success of his diet and asked him how he’s been doing.

When RG looked at the pharmacist to respond, his expression changed.

“I’m not doing well. I just got a call from my doctor’s nurse who said to come in immediately. They just got the results of my blood work and my serum creatinine (sCr) is elevated, and I’m going into renal failure,” RG said. “I’m so discouraged. I did all this work to get healthy for nothing. My father went into kidney failure because he had high blood pressure, and I didn’t want that to happen to me. How did this happen?”

Mystery: How did getting healthy and losing weight result in RG going into kidney failure?

Solution: The lisinopril dose caused the kidney failure. The dose needed to be adjusted down once RG lost weight and his hypertension had been resolved or mitigated. The good news is that the elevation in sCr is reversible if caught in time.

Lisinopril, as well as other angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), are capable of preventing and causing kidney failure. The blood pressure in the kidneys needs to be in balance, remaining both not too high and not too low.

Millions of hypertensive people are spared the fate of renal failure due to the development of lisinopril and other ACE inhibitors. However, a very small percentage of these people also go into renal failure when poor renal perfusion occurs and the ACE inhibitor dose is not properly adjusted or discontinued as necessary.

When working appropriately, tubules within the kidneys function by filtering the blood of impurities and producing urine. However, these delicate tubules can easily become damaged by high blood pressure. In such circumstances, lisinopril protects the kidneys from damage by lowering the blood pressure so that the tubules can continue functioning.

On the other hand, if the blood pressure then drops too low for too long in the kidneys, then blood flow is reduced, and the renal tissues can become starved of oxygen and other nutrients. However, before renal failure sets in, the sCr level rises, indicating a low filtration pressure. At that point, a dose reduction of an ACE inhibitor or discontinuation of the drug can normalize the sCr.

Normally, the renal arteries constrict and relax to maintain balanced blood pressure. However, lisinopril and similar drugs relax the renal arteries to the point that they cannot constrict properly even when blood flow is low. The compensatory mechanism that then maintains homeostasis in kidneys is somewhat lost under these circumstances.

For these reasons, patients who take diabetic and hypertension medication and are experiencing dramatic weight loss should be advised to monitor their blood sugar and blood pressure at home and work closely with their doctor. The best method available for the monitoring of low blood pressure in the kidneys is through the use of a sCr blood test.

REFERENCE

Navis G, Faber HJ, de Zeeuw D, de Jong PE. ACE inhibitors and the kidney. A risk-benefit assessment. Drug Saf. 1996 Sep;15(3):200-11. doi: 10.2165/00002018-199615030-00005. PMID: 8879974.