Uremic pancreatitis following routine initiation of losartan in advanced chronic kidney disease: A case report

Abstract

Angiotensin receptor blockers (ARBs) are commonly used to slow the progression of chronic kidney disease (CKD) but may worsen renal function in advanced kidney disease. We describe a 35-year-old man with stage 4 CKD who developed acute kidney injury shortly after starting an ARB, followed by severe abdominal pain and biochemical evidence of pancreatitis. Imaging excluded gallstones and ductal obstruction. Laboratory studies ruled out hypertriglyceridemia and hypercalcemia. He was found to have profound azotemia, consistent with uremia. His abdominal pain and elevated pancreatic enzymes improved rapidly with hemodialysis, supporting a diagnosis of uremic pancreatitis rather than direct losartan toxicity. Uremic pancreatitis is rare and usually described in patients with end-stage renal disease; its occurrence in earlier CKD stages is underrecognized. This case highlights uremia as a rare cause of pancreatitis that should be considered in the setting of worsening azotemia and abdominal pain. Patients should be carefully monitored when initiating ARBs in the setting of advanced CKD.

Introduction

Angiotensin receptor blockers (ARBs) are widely used to slow the progression of chronic kidney disease (CKD), particularly in patients with albuminuria. ¹ However, they may worsen renal function in advanced CKD by reducing glomerular filtration through efferent arteriolar dilation. Severe azotemia in the setting of worsening renal function may lead to systemic manifestations of uremia, including gastrointestinal and cardiovascular complications. Severe azotemia from impaired clearance of nitrogenous waste has rarely been associated with uremic pancreatitis—a complication that remains underrecognized. ² We present a case of presumed uremic pancreatitis that developed shortly after losartan initiation in a patient with advanced CKD.

Case

A 35-year-old male with a history of stage 4 CKD (biopsy-proven IgA nephropathy with 60% interstitial fibrosis and tubular atrophy 2 years prior to presentation; baseline creatinine 3.7 mg/dL, eGFR 21 mL/min/1.73 m²), nephrolithiasis, and hypertension presented to the emergency department with a 2-week history of epigastric pain, severe nausea, and vomiting without jaundice. Two weeks prior to presentation, he began taking losartan 100 mg and amlodipine 5 mg daily to manage worsening proteinuria and hypertension, but otherwise denied taking any additional medications. Three days later, he began to experience mild nausea and epigastric discomfort. Over the next 11 days, the symptoms worsened to include more pronounced nausea, persistent vomiting, decreased urine output, and severe abdominal pain (Figure 1). He denied significant use of alcohol, tobacco, or supplements. He also denied any recent procedures or trauma.

Figure 1.

Timeline of symptom progression.

On admission, he was hemodynamically stable and afebrile with initial vital signs notable for heart rate 87 beats per min, blood pressure 145/79 mmHg, temperature 36.5°C, respiratory rate 19 breaths per min, and peripheral oxygen saturation 100% on room air. Physical examination was notable for asterixis, dry mucous membranes, and no edema. Initial laboratory evaluation demonstrated leukocytosis (white blood cell count 16.42 × 10³/µL), anemia (hemoglobin 10.5 g/dL; hematocrit 28.3%), and thrombocytopenia (platelets 140 × 10³/µL). Lactate was within normal limits (0.7 mmol/L). Venous blood gas was notable for pH 7.13, partial pressure of CO₂ 24 mmHg, and bicarbonate 8 mmol/L. Serum chemistries revealed severe metabolic derangement with bicarbonate 7 mmol/L and a markedly elevated anion gap of 37. Blood urea nitrogen was 231 mg/dL and serum creatinine was 28 mg/dL, representing profound acute kidney injury superimposed on CKD. Lipase was elevated at 743 U/L. Liver chemistries were within normal limits. Serum potassium was 4.6 mmol/L, and total serum calcium was 4.8 mg/dL (Table 1). Antinuclear antibody (ANA), triglycerides (121 mg/dL), and hepatitis B serologies were within normal limits.

Table 1.

Laboratory values on admission.

Test	Initial value	Reference range
Serum chemistries
Sodium	119	135–145 mmol/L
Potassium	4.6	3.6–5.0 mmol/L
Chloride	75	98–100 mmol/L
CO2	7	22–31 mmol/L
Anion gap	37	6–16 mmol/L
BUN	231	6–23 mg/dL
Creatinine	27.95	0.67–1.17 mg/dL
Total calcium	4.8	8.4–10.2 mg/dL
Complete blood count
White blood cell count	16.42	4.22–10.33 × 10³/µL
Neutrophils, absolute	14.93	1.98–6.59 × 10³/µL
Lymphocytes, absolute	0.47	1.30–4.07 × 10³/µL
Red blood cell count	3.74	4.27–5.99 × 10³/µL
Hemoglobin	10.5	13.2–16.9 g/dL
Hematocrit	28.3	39.6–50.2%
Platelet	140	160–383 × 10³/µL
Liver function tests
ALT	10	10–50 Units/L
AST	18	10–50 Units/L
Alkaline phosphatase	118	40–129 Units/L
Lipid profile
Total cholesterol	199	120–199 mg/dL
HDL	46	40–80 mg/dL
LDL, Calc	129	⩽99 mg/dL
Triglycerides	121	50–150 mg/dL
Venous blood gas and lactate
pH	7.13	7.31–7.41
PCO2	24	30–50 mmHg
HCO3	8	24–28 mmol/L
Lactate	0.7	0.5–2.2 mmol/L
Additional notable results
Creatine kinase	1640	39–308 Units/L
High-sensitivity troponin	336	⩽53 ng/L
NT-proBNP	41,296	<125 pg/mL
Lipase	743	7–59 Units/L
Hepatitis B surface antigen	Nonreactive	<8.00 mIU/mL
Hepatitis B core antigen	Nonreactive
ANA	Negative

LDL: low-density lipoprotein; HDL: high-density lipoprotein; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ALP: alkaline phosphatase.

The right upper quadrant ultrasound was unremarkable. Computed tomography of the abdomen and pelvis without contrast demonstrated peripancreatic stranding without gallstones, ductal dilation, or obstruction (Supplemental Figure 1). Magnetic resonance cholangiopancreatography (MRCP) showed no pancreatic or biliary ductal dilatation and demonstrated peripancreatic trace-free fluid with no organized collection, bulky pancreatic morphology, and homogeneous pancreatic enhancement consistent with pancreatitis.

Given the severity of high–anion gap metabolic acidosis, profound azotemia, and evidence of uremia (asterixis and pericardial friction rub), the patient was admitted to the medical intensive care unit for management of acute pancreatitis and acute-on-chronic renal failure. Losartan and amlodipine were discontinued. He was treated with intravenous fluids, bowel rest, and urgent initiation of hemodialysis due to severe metabolic derangements, metabolic acidosis, and hyponatremia.

The patient reported improvement in abdominal pain after two hemodialysis sessions by hospital day 2, coinciding with a reduction in BUN from 231 to 140 mg/dL. Symptoms continued to improve over 8 days with a total of 5 dialysis sessions (Table 2). Prior to discharge, he was classified as dialysis-dependent end-stage renal disease (ESRD, eGFR 5 mL/min/1.73 m²). He continues outpatient maintenance hemodialysis and is undergoing renal transplant evaluation.

Table 2.

Serum chemistry trends and HD session details.

Hospital day	HD session details			Labs prior to each HD session
	HD session	Ultrafiltration (liters removed)	HD duration (h)	BUN (mg/dL)	Creatinine (mg/dL)	Bicarbonate (mmol/L)	Potassium (mmol/L)	Total calcium (mg/dL)
2*	1	0	2	219	25.47	10	3.3	5.5
	2	0	2.5	140	16.93	21	3.4	7.8
4	3	1	3	92	13.76	23	4.1	8.3
6	4	1	3.5	34	8.18	30	4.1	8.1
8	5	1.5	3.5	54	10.11	26	4.4	8.1

Each row represents laboratory values prior to the subsequent hemodialysis session on that day. *On hospital day 2, the patient received 2 sessions of hemodialysis. HD: hemodialysis.

Discussion

Uremic pancreatitis is a rare and underrecognized complication of CKD. ² Proposed mechanisms include the accumulation of toxic nitrogenous metabolites and microvascular dysfunction. ² Although more commonly associated with ESRD patients on peritoneal dialysis, it may occur in earlier stages of CKD if kidney function acutely declines. ³ This case uniquely demonstrates uremia in stage 4 CKD, rather than in ESRD, which is more commonly reported. ³ In our patient with baseline CKD stage 4, the combined effect of efferent arteriolar dilation with losartan initiation and afferent arteriolar dilation from amlodipine may have precipitated a sharp decline in the glomerular filtration rate. Physicians should be aware of the risk of uremic pancreatitis in patients with CKD not yet started on dialysis. Symptoms of abdominal pain, nausea, and vomiting are non-specific and are present in both uremia and pancreatitis, which may explain why uremic pancreatitis may be underdiagnosed. Furthermore, elevated levels of lipase and amylase are common findings in CKD due to impaired clearance, which may obscure any underlying pancreatitis. ³ However, as in this case, the final diagnosis of pancreatitis can be further confirmed by the presence of abdominal pain and radiographic findings consistent with pancreatitis.

One alternative explanation for our patients’ presentation was possible direct pancreatic toxicity from losartan. Using the Naranjo Adverse Drug Reaction Probability Scale, ⁴ the patient’s score was 3, suggesting a possible association with losartan initiation. However, several clinical features make a primary uremic process more plausible. The patient presented with a blood urea nitrogen level approximately 10 times the upper limit of normal, consistent with severe uremia at baseline. Both the drug losartan and its active metabolite E-3174 are >95% protein-bound and not dialyzable. E-3174 has a terminal half-life of up to 9 h, with detectable drug levels at >24 h, ⁵ suggesting that symptoms may have persisted after hemodialysis if losartan were the primary suspect. Prior reports of losartan-induced pancreatitis describe clinical resolution within 5 days of discontinuation alone.^3,6 By contrast, our patient experienced significant improvement after only 1 day with 2 sessions of dialysis. The temporal improvement closely aligned with uremic clearance rather than pharmacokinetic elimination of losartan. ⁵ Taken together, while a drug-related contribution cannot be entirely excluded, the overall clinical course favors severe uremia as the more likely primary driver of this patient’s acute deterioration. Rechallenge with an ARB was not performed and was deemed inappropriate given the severity of the initial presentation, including profound azotemia and life-threatening metabolic acidosis. Amlodipine was safely reintroduced on hospital day 6 without complication. While our inability to rule out losartan-induced pancreatitis is a limitation, the pharmacokinetics of losartan and its rapid improvement with dialysis support uremia as the primary driver of his pancreatitis.

One additional limitation of our findings is that we did not evaluate serum IgG4 levels to definitively rule out a common cause of autoimmune pancreatitis. However, IgG4-related pancreatitis is classically associated with beading of the biliary tree, which can be seen on MRCP. This patient’s MRCP did not show any structural abnormalities, which reduces the possibility of IgG4-related pancreatitis. ⁷ Finally, as a single-patient case report, the generalizability is limited and additional research is needed to evaluate the prevalence of uremic pancreatitis in patients with CKD.

Conclusion

This case highlights the importance of close monitoring after ARB initiation in patients with advanced CKD. In summary, we offer the following suggestions to clinicians caring for patients with advanced CKD:

• While ARBs offer nephroprotective benefits in early stages, they may paradoxically worsen renal function in patients with advanced CKD.

• Clinicians should closely monitor renal function and electrolytes, including serum creatinine and potassium, within 1–2 weeks of initiating or escalating an angiotensin-converting enzyme inhibitor or ARB in patients with advanced CKD (eGFR <30 mL/min/1.73 m²). Earlier testing may be warranted in high-risk individuals.

• In addition, patients should receive explicit anticipatory guidance for acute illness to temporarily hold these medications during periods of vomiting, diarrhea, or poor oral intake to reduce the risk of prerenal azotemia and further renal injury. ⁸

In patients with severe azotemia and pancreatitis of unclear etiology, the diagnosis of uremic pancreatitis should be considered.

Supplemental Material

sj-pdf-1-sco-10.1177_2050313X261449105 – Supplemental material for Uremic pancreatitis following routine initiation of losartan in advanced chronic kidney disease: A case report

Supplemental material, sj-pdf-1-sco-10.1177_2050313X261449105 for Uremic pancreatitis following routine initiation of losartan in advanced chronic kidney disease: A case report by Victoria C. Yan, Abhi N. Deverakonda, Alex R. Jones, Joseph R. Berger, Rebecca P. Liu, Fredy Calderon, Dorothy J. Patterson and Nicole Oakman in SAGE Open Medical Case Reports