scholarly journals Hemoglobin inhibits albumin uptake by proximal tubule cells: implications for sickle cell disease

2017 ◽  
Vol 312 (6) ◽  
pp. C733-C740 ◽  
Author(s):  
Megan L. Eshbach ◽  
Amandeep Kaur ◽  
Youssef Rbaibi ◽  
Jesús Tejero ◽  
Ora A. Weisz
Keyword(s):  
Sickle Cell Disease ◽  
Proximal Tubule ◽  
Sickle Cell ◽  
Prolonged Exposure ◽  
Tubular Dysfunction ◽  
Cell Disease ◽  
Tubular Proteinuria ◽  
Proximal Tubule Cells ◽  
Dimer Interface ◽  
Hemolytic Crisis

Proximal tubule (PT) dysfunction, including tubular proteinuria, is a significant complication in young sickle cell disease (SCD) that can eventually lead to chronic kidney disease. Hemoglobin (Hb) dimers released from red blood cells upon hemolysis are filtered into the kidney and internalized by megalin/cubilin receptors into PT cells. The PT is especially sensitive to heme toxicity, and tubular dysfunction in SCD is thought to result from prolonged exposure to filtered Hb. Here we show that concentrations of Hb predicted to enter the tubule lumen during hemolytic crisis competitively inhibit the uptake of another megalin/cubilin ligand (albumin) by PT cells. These effects were independent of heme reduction state. The Glu7Val mutant of Hb that causes SCD was equally effective at inhibiting albumin uptake compared with wild-type Hb. Addition of the Hb scavenger haptoglobin (Hpt) restored albumin uptake in the presence of Hb, suggesting that Hpt binding to the Hb αβ dimer-dimer interface interferes with Hb binding to megalin/cubilin. BLAST searches and structural modeling analyses revealed regions of similarity between Hb and albumin that map to this region and may represent sites of Hb interaction with megalin/cubilin. Our studies suggest that impaired endocytosis of megalin/cubilin ligands, rather than heme toxicity, may be the cause of tubular proteinuria in SCD patients. Additionally, loss of these filtered proteins into the urine may contribute to the extra-renal pathogenesis of SCD.

scholarly journals Alternating and Concurrent True Hyperkalemia and Pseudohyperkalemia in Adult Sickle Cell Disease

2021 ◽  
Vol 12 (2) ◽  
pp. e0018
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Cell Disease ◽  
Hemolytic Crisis ◽  
Renal Tubular ◽  
Potassium Binders ◽  
Sodium Zirconium Cyclosilicate

Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients, and renal manifestations of SCN include renal ischemia, microinfarcts, renal papillary necrosis, and renal tubular abnormalities with variable clinical presentations. Intravascular hemolysis and reduced glomerular filtration rate with renal tubular dysfunction predispose to true hyperkalemia. Hemolytic crisis can be complicated by sepsis, leading to significant degrees of thrombocytosis, and thrombocytosis is a well-defined cause of pseudohyperkalemia. We describe a 40-year-old African American male patient with sickle cell anemia who exhibited alternating episodes of true hyperkalemia and pseudohyperkalemia, during consecutive hospital admissions. Clearly, true hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate and intensive treatment of pseudohyperkalemia leading to severe hypokalemia is also potentially lethal. The need for this caution is most imperative with the recent introduction of the safer and more potent potassium binders, patiromer and sodium zirconium cyclosilicate.

scholarly journals Hemoglobin Inhibits Uptake of Filtered Proteins by Proximal Tubule Cells: Implications for Sickle Cell Disease and Vitamin D Status

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Megan L. Eshbach ◽  
Amandeep Kaur ◽  
Youssef Rbaibi ◽  
Yash Agarwal ◽  
Qiangmin Zhang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sickle Cell Disease ◽  
Proximal Tubule ◽  
Sickle Cell ◽  
Vitamin D Status ◽  
Cell Disease ◽  
Proximal Tubule Cells ◽  
Tubule Cells

scholarly journals EVALUATION OF RENAL CHANGES IN SICKLE CELL DISEASE IN A REFERRAL GOVERNMENT INSTITUTE OF SOUTHERN ODISHA

2021 ◽  
pp. 90-95
Author(s):  
BIJAYA KUMAR BEHERA ◽  
SUSANTA SEKHAR BEHERA ◽  
SUKANTA KUMAR JENA ◽  
RAKESH MOHANTY ◽  
NISARG BEHERA
Keyword(s):  
Sickle Cell Disease ◽  
Epithelial Cell ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Renal Involvement ◽  
Systemic Hypertension ◽  
Structural Abnormality ◽  
Tubular Dysfunction ◽  
Cell Disease ◽  
Renal Changes

Objective: The objective of the study was to study various renal manifestations in sickle cell disease (SCD) and to establish a cause and effect relationship with the evaluation of risk factors. Methods: This prospective observational cross-sectional study was conducted on 82 SCD patients belonging to the age group of 15–50 years of both the genders over a period of 2 years from January 2019 to December 2020 in MKCG Medical College and Hospital, Berhampur, Odisha, India. Eighty-two patients, 32 (39.02%) having sickle cell anemia (SCA) and 50 (60.98%) having sickle cell trait (SCT), admitted to medicine and nephrology wards of the hospital were included in this study. SCD patients with other hemolytic anemia and with renal congenital/structural abnormality and patients with systemic diseases such as diabetes mellitus, systemic hypertension, and systemic lupus erythematosus were excluded from the study. Various laboratory investigations such as complete blood count, hemoglobin (Hb), serum sodium, serum potassium, serum urea, serum creatinine, fasting blood sugar, erythrocyte sedimentation rate, liver function test, urine routine, and microscopic test were carried out. Diagnosis of SCD patients was based on sickling test and high-performance liquid chromatography testing. Radiologic imaging (Sonography for renal changes) was done at radiodiagnosis department of the hospital. Results: Glomerular and tubular dysfunction was more in SCA (Hb SS) patients than SCT (Hb AS) patients and the abnormality was more in patients in crisis. Albuminuria in 78.12%, hematuria in 46.87%, cast and crystal in 28.12%, epithelial cell in 31.25%, and hyposthenuria in 56.25% were found in SCA patients. In SCT patients, albuminuria in 38%, hematuria in 16%, cast and crystal in 22%, epithelial cell in 12%, and hyposthenuria in 24% were found. All the above findings were more in percentages in crisis patients of both the groups. In SCA, 37.5% and in SCT, 2% were found to have chronic kidney disease. Conclusion: Renal involvement in the form of glomerular and tubular dysfunction occur in SCD and more in crisis patients, leading to renal complications, and end-stage renal disease.

scholarly journals MO218ALTERNATING EPISODES OF TRUE HYPERKALEMIA AND PSEUDOHYPERKALEMIA IN ADULT SICKLE CELL DISEASE - A NEPHROLOGIST'S DILEMA

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Macaulay Onuigbo ◽  
Sarah Sherman ◽  
Heng Tan
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Potassium ◽  
Hospital Admissions ◽  
Adult Patients ◽  
Electrolyte Imbalance ◽  
Cell Disease ◽  
Clinical Scenarios ◽  
Hemolytic Crisis ◽  
Potassium Binders

Abstract Background and Aims To illustrate the phenomenon of alternating true hyperkalemia and pseudohyperkalemia in adult sickle cell disease. Method Case Report Results Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients. The presence of sickled erythrocytes in the renal medullary vessels is the hallmark of the disease and renal manifestations include renal ischemia, microinfarcts, renal papillary necrosis and renal tubular abnormalities with variable clinical presentations. Furthermore, acute hemolytic crisis can be complicated by sepsis. Hemolysis, specifically, intravascular hemolysis, can produce hyperkalemia. Additionally, reduced glomerular filtration rate from SCN predisposes to hyperkalemia. Pseudo-hyperkalemia was first reported by Hartmann and Mellinkoff in 1955 as a marked elevation of serum potassium levels in the absence of clinical evidence of electrolyte imbalance. In pseudohyperkalmia, simultaneously estimated serum potassium exceeds plasma potassium by >0.4 mmol/L. This is often associated with moderate to severe thrombocytosis or leukocytosis. Clearly, hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate treatment of pseudo-hyperkalemia leading to hypokalemia is also equally potentially lethal. We describe a 40-yo African American male patient with sickle cell anemia who exhibited alternating episodes of hyperkalemia and pseudo-hyperkalemia, during consecutive hospital admissions. Pseudohyperkalemia was associated with severe thrombocytosis complicating sepsis. EKG was normal despite measured serum potassium of 6.7 mmol/L (Figure). Conclusion We believe that this is the first report of adult SCD demonstrating alternating cycles of true hyperkalemia and pseudo-hyperkalemia at different times. We must draw attention to the new availability of the new potassium binders, Patiromer and sodium zirconium cyclosilicate. We would advocate for caution in the use of these potent potassium binders and to always give consideration to the presence of pseudo-hyperkalemia under appropriate clinical scenarios. We posit that providers managing adult patients with sickle cell disease must be aware of such a phenomenon to avoid the dangers of overtreatment of episodes of pseudo-hyperkalemia in such patients.

scholarly journals Renal Tubular Dysfunction in Sickle Cell Disease

2013 ◽  
Vol 38 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Geraldo B. Silva Junior ◽  
Ana Patrícia F. Vieira ◽  
Amanda X. Couto Bem ◽  
Marília P. Alves ◽  
Gdayllon C. Meneses ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Cell Disease ◽  
Renal Tubular

Proximal tubule albumin uptake – potential role for endothelin system in sickle cell disease mice

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Malgorzata Kasztan ◽  
Hasan Alrefai ◽  
Crystal Taylor ◽  
David M. Pollock
Keyword(s):  
Sickle Cell Disease ◽  
Proximal Tubule ◽  
Sickle Cell ◽  
Potential Role ◽  
Cell Disease ◽  
Endothelin System

Sickle-cell disease and the kidney

2010 ◽  
pp. 4069-4071
Author(s):  
G R Serjeant
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Nocturnal Enuresis ◽  
Renal Medulla ◽  
Vascular Damage ◽  
Tubular Dysfunction ◽  
Cell Disease ◽  
Homozygous Sickle Cell Disease

The vasa rectae system of the renal medulla is uniquely conducive to sickling, which leads to vascular damage and tubular dysfunction, including an inability to concentrate the urine. Renal presentations include nocturnal enuresis, haematuria (thought to be due to ischaemic lesions of the papillae, including papillary necrosis), and gradually progressive chronic renal failure, which is an important cause of morbidity and death in patients with homozygous sickle-cell disease over the age of 40 years....

scholarly journals Hemoglobin alters vitamin carrier uptake and vitamin D metabolism in proximal tubule cells: implications for sickle cell disease

2019 ◽  
Vol 317 (5) ◽  
pp. C993-C1000 ◽  
Author(s):  
Megan L. Gliozzi ◽  
Youssef Rbaibi ◽  
Kimberly R. Long ◽  
Dario A. Vitturi ◽  
Ora A. Weisz
Keyword(s):  
Vitamin D ◽  
Sickle Cell Disease ◽  
Proximal Tubule ◽  
Vitamin D Deficiency ◽  
Sickle Cell ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Mrna Levels ◽  
Cell Disease ◽  
Vitamin D Metabolism

Kidney disease, including proximal tubule (PT) dysfunction, and vitamin D deficiency are among the most prevalent complications in sickle cell disease (SCD) patients. Although these two comorbidities have never been linked in SCD, the PT is the primary site for activation of vitamin D. Precursor 25-hydroxyvitamin D [25(OH)D] bound to vitamin D-binding protein (DBP) is taken up by PT cells via megalin/cubilin receptors, hydroxylated to the active 1,25-dihydroxyvitamin D [1,25(OH)2D] form, and released into the bloodstream. We tested the hypothesis that cell-free hemoglobin (Hb) filtered into the PT lumen impairs vitamin D uptake and metabolism. Hb at concentrations expected to be chronically present in the ultrafiltrate of SCD patients competed directly with DBP for apical uptake by PT cells. By contrast, uptake of retinol binding protein was impaired only at considerably higher Hb concentrations. Prolonged exposure to Hb led to increased oxidative stress in PT cells and to a selective increase in mRNA levels of the CYP27B1 hydroxylase, although protein levels were unchanged. Hb exposure also impaired vitamin D metabolism in PT cells, resulting in reduced ratio of 1,25(OH)2D:25(OH)D. Moreover, plasma levels of 1,25(OH)2D were reduced in a mouse model of SCD. Together, our data suggest that Hb released by chronic hemolysis has multiple effects on PT function that contribute to vitamin D deficiency in SCD patients.

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