Anemia Biomarkers in Pregnant People with Pyelonephritis

Abstract

Objective

Anemia is observed in 30% of pregnancies with pyelonephritis, yet little is known about the underlying etiology. Erythropoietin (EPO) is renally produced in response to hypoxic and inflammatory conditions. Changes in serum EPO have been demonstrated in infectious conditions in the nonpregnant population. EPO levels have been measured in healthy pregnancy cohorts, but little is known about patterns in the setting of renal inflammation. Our primary objective was to compare EPO levels in pregnant patients at diagnosis of acute pyelonephritis to established trimester-specific norms. Secondary objectives included assessing iron deficiency and hemolysis markers as alternate etiologies of anemia.

Study Design

Prospective cohort study of pregnant people aged ≥ 18 years diagnosed with pyelonephritis, defined as the presence of urinary tract infection symptoms plus flank pain, fever, or nausea/vomiting. Blood samples including EPO, iron, transferrin, lactate dehydrogenase (LDH), and haptoglobin were obtained within 72 hours of diagnosis. Demographics and clinical data were abstracted from medical records. Wilcoxon Signed-Rank test compared study EPO levels to noninfected pregnancy values established in the literature. Secondary outcomes included number of patients with iron/hemolysis laboratories within trimester-specific reference ranges.

Results

The study cohort included 17 patients with pyelonephritis in the second or third-trimester. There were no eligible first-trimester patients during the study period. Anemia was present on admission in 35.3% (6/17) of patients. EPO levels were significantly higher in pyelonephritis patients during the second-trimester compared with literature-established EPO levels in noninfected controls: 48.6 versus 10.6 mU/mL, (p = 0.0001). Secondary analysis demonstrated normal iron and haptoglobin levels in most patients, and normal LDH in all patients.

Conclusion

EPO levels in pregnant pyelonephritis patients were significantly higher compared with trimester-specific normative levels established in the literature. Evaluation of iron and hemolysis studies showed inconsistent results but were often normal. This pilot study may suggest a relationship between ineffective erythropoiesis and renal inflammation in pregnancies complicated by pyelonephritis.

Key Points

• Anemia is present in 30 to 50% of pregnant patients with pyelonephritis.

• EPO was higher in the pyelonephritis cohort compared with normal pregnancy values.

• Iron and haptoglobin were normal in most patients, LDH was normal in all patients.

Keywords

anemia - erythropoietin - inflammation - pyelonephritis - urinary tract infection - hemolysis

Publikationsverlauf

Eingereicht: 01. November 2024

Angenommen: 26. Februar 2025

Artikel online veröffentlicht:
27. März 2025

• References

• 1 Hill JB, Sheffield JS, McIntire DD, Wendel Jr GD. Acute pyelonephritis in pregnancy. Obstet Gynecol 2005; 105 (01) 18-23
• 2 Beydoun SN. Morphologic changes in the renal tract in pregnancy. Clin Obstet Gynecol 1985; 28 (02) 249-256
• 3 Cox SM, Shelburne P, Mason R, Guss S, Cunningham FG. Mechanisms of hemolysis and anemia associated with acute antepartum pyelonephritis. Am J Obstet Gynecol 1991; 164 (02) 587-590
• 4 Dawkins JC, Fletcher HM, Rattray CA, Reid M, Gordon-Strachan G. Acute pyelonephritis in pregnancy: a retrospective descriptive hospital based-study. ISRN Obstet Gynecol 2012; 2012: 519321
• 5 Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood 2019; 133 (01) 40-50
• 6 Morceau F, Dicato M, Diederich M. Pro-inflammatory cytokine-mediated anemia: regarding molecular mechanisms of erythropoiesis. Mediators Inflamm 2009; 2009: 405016
• 7 Rivkin M, Simerzin A, Zorde-Khvalevsky E. et al. Inflammation-induced expression and secretion of microRNA 122 leads to reduced blood levels of kidney-derived erythropoietin and anemia. Gastroenterology 2016; 151 (05) 999-1010.e3
• 8 Joosten E, Van Hove L, Lesaffre E. et al. Serum erythropoietin levels in elderly inpatients with anemia of chronic disorders and iron deficiency anemia. J Am Geriatr Soc 1993; 41 (12) 1301-1304
• 9 Vora M, Gruslin A. Erythropoietin in obstetrics. Obstet Gynecol Surv 1998; 53 (08) 500-508
• 10 Beguin Y, Lipscei G, Thoumsin H, Fillet G. Blunted erythropoietin production and decreased erythropoiesis in early pregnancy. Blood 1991; 78 (01) 89-93
• 11 Cavenee MR, Cox SM, Mason R, Cunningham FG. Erythropoietin in pregnancies complicated by pyelonephritis. Obstet Gynecol 1994; 84 (02) 252-254
• 12 Anemia in Pregnancy. Anemia in pregnancy: ACOG practice bulletin, number 233. Obstet Gynecol 2021; 138 (02) e55-e64
• 13 Harstad TW, Mason RA, Cox SM. Serum erythropoietin quantitation in pregnancy using an enzyme-linked immunoassay. Am J Perinatol 1992; 9 (04) 233-235
• 14 Morton A. Hematologic normal ranges in pregnancy. In: Chen KK. ed. Maternal Medical Health and Disorders in Pregnancy. London: Global Women's Medicine; 2021
• 15 Lipkin GW, Kendall RG, Russon LJ, Turney JH, Norfolk DR, Brownjohn AM. Erythropoietin deficiency in acute renal failure. Nephrol Dial Transplant 1990; 5 (11) 920-922
• 16 Turner G, Gibson OR, Watt PW, Pringle JSM, Richardson AJ, Maxwell NS. The time course of endogenous erythropoietin, IL-6, and TNFα in response to acute hypoxic exposures. Scand J Med Sci Sports 2017; 27 (07) 714-723