Transient Elevations of Microalbuminuria May Represent a Marker of Systemic Vascular Injury in Sickle Cell Disease Patients.
Authors: Hrinczenko Borys , Schelling Jeffrey R. 
Published: October 2019

Abstract 4611

Sickle cell disease (SCD) is a genetic blood disorder of hemoglobin function resulting in severe morbidity and early mortality. Hemolysis and vascular obstruction, endothelial activation and dysfunction, and inflammation, are hallmarks of this disease contributing to a chronic and progressive pathophysiology. Renal complications include hematuria, proteinuria, chronic renal insufficiency, and end stage renal disease. Several studies in SCD patients have shown that microalbuminuria may be a potential marker of progression to chronic renal disease. Also, microalbuminuria has been proposed as a marker of worsening outcome in diabetes, cardiovascular disease, cancer, lymphoma, and clotting. The Steno hypothesis (Diabetologia 1989; 32: 219) proposed that albuminuria is a biomarker of systemic vascular damage in diabetics, not just a marker of localized renal disease but also of retinopathy and macroangiopathy. We propose that the Steno hypothesis may also apply to SCD patients in that albuminuria may reflect systemic vascular disease injury besides potential renal impairment. From a cohort of 33 SCD patients in a county hospital hematology clinic, 11 patients were admitted through the emergency department with acute vaso-occlusive pain crisis over a one month period, and all were evaluated for microalbuminuria. [7 males, 4 females; 7 HbSS, 3 HbSC, 1 HbS beta-thalassemia; median age 41.7 years (range, 20 - 59 years), median hospital stay of 3.5 days (range, 2 – 8 days)]. None of the patients had renal insufficiency. Hospitalized patients were treated with intravenous fluids and intravenous narcotics. The median albuminuria value at admission was 21 mg/g creatinine. During hospitalization, 6 patients remained normoalbuminuric (<30 mg/g creatinine) during their entire hospital stay, 5 patients (3 HbSS, 2 HbSC) were microalbuminuric (30 – 299 mg/g creatinine), and none were macroalbuminuric (> 300 mg/g creatinine). Three of the microalbuminuric patients were followed with daily early morning albuminuria determinations. Two of those patients displayed a peak microalbuminuria level followed by a progressive drop at the time of hospital discharge. For instance, one HbSS patient was hospitalized for 8 days and at admission his albuminuria level was 69 mg/g creatinine. His daily microalbuminuria level progressively rose and peaked at 100 mg/g creatinine on hospital day 4, and then decreased daily to 86 mg/g creatinine at discharge on hospital day 8. Another microalbuminuric HbSC patient presented on admission with a microalbuminuria level of 67 mg/g creatinine. His microalbuminuria level peaked at 98 mg/g creatinine on hospital day 2 and then dropped to 3 mg/g creatinine at discharge on hospital day 4. These patients had elevations of their daily albuminuria values from initial baseline values during a pain crisis which peaked and then decreased as their crisis resolved and were discharged from the hospital. Only a subset of SCD patients hospitalized in pain crisis showed evanescent increases in albuminuria levels during a pain crisis. This incremental elevation of albuminuria represents an extension of the Steno hypothesis, in that it may serve as a sensitive biomarker for vaso-occlusive pain crisis, a unique form of systemic vascular endothelial injury. Furthermore, a decrease in microalbuminuria, or even a drop to normoalbuminuria, in SCD patients may be a useful marker to assess response to therapy. A prospective study on SCD patients with normoalbuminuria and microalbuminuria is needed to confirm this hypothesis.

Disclosures:

No relevant conflicts of interest to declare.