# The sick-day cascade

One illness can produce several kidney and acid–base problems

Andrew Bland, MD, FACP, FAAP · October 19, 2026

[Open visual and zoom](https://urinenephrology.org/visual-reference/case-sick-day-cascade.html)

Vomiting, diarrhea, and poor intake can reduce renal perfusion. NSAIDs, ACE inhibitors or ARBs, and diuretics can compound the hemodynamic problem. Illness and fasting during SGLT2 therapy raise ketoacidosis risk. Vomiting may add metabolic alkalosis, while diarrhea may add normal-gap acidosis.

## Perfusion and medication effects

Volume depletion lowers renal perfusion. NSAIDs reduce prostaglandin-supported afferent dilation; ACE inhibitors and ARBs reduce angiotensin-mediated efferent constriction. Diuretics may add volume loss. Prolonged severe hypoperfusion can progress to tubular injury. These mechanisms explain why a beneficial chronic treatment may require reassessment during an acute illness.

## Ketones and a misleading glucose

Illness, reduced intake, and SGLT2 therapy can combine to produce ketoacidosis with only modest glucose elevation. Use blood ketones and the acid–base findings, rather than excluding DKA because glucose is not markedly elevated. Serum potassium can be normal or high despite total-body potassium depletion.

## More than one acid–base process

Vomiting can produce chloride-depletion alkalosis, while diarrhea produces bicarbonate loss and normal-gap acidosis. Ketone accumulation adds an anion-gap process. Read pH, bicarbonate, anion gap, and expected respiratory compensation together. A personalized sick-day plan specifies temporary holds, when to call, and how treatment will restart; transplant immunosuppression and essential insulin need specific clinical direction.

## Discuss

Can a near-normal pH or a mildly elevated glucose exclude a serious sick-day problem?

No. Mixed acid–base processes can partly offset one another, and SGLT2-associated ketoacidosis may occur without marked hyperglycemia. Review the full pattern, ketones, volume status, medication timing, and kidney-function trend.

## Sources

- [2024 international consensus on hyperglycemic crises](https://pubmed.ncbi.nlm.nih.gov/39052901/)
- [Lapi et al.: NSAID, RAAS-blocker, and diuretic combinations and AKI](https://pubmed.ncbi.nlm.nih.gov/23299844/)

## Related cases

- [Case 03: The Sick Day That Wasn't Held](https://urinenephrology.org/2025_UDPA_Lectures_Live/case-based-lectures/cbl-03-the-sick-day-that-wasn-t-held.html#case-visual-summary)
- [Case 05: The Salt Substitute](https://urinenephrology.org/2025_UDPA_Lectures_Live/case-based-lectures/cbl-05-the-salt-substitute.html#case-visual-summary)
- [Case 10: Two Dark Urines](https://urinenephrology.org/2025_UDPA_Lectures_Live/case-based-lectures/cbl-10-two-dark-urines.html#case-visual-summary)