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Sickle Cell Nephropathy

Sickle cell nephropathy is an important cause of morbidity and mortality in patients with sickle cell disease, an autosomal recessive genetic disorder of impaired hemoglobin synthesis. Nephropathy stems from progressive obstruction of renal vessels, subsequent hypoxia, and ischemia of the renal parenchyma, eventually causing fibrosis, glomerulosclerosis, and renal failure. Hematuria, proteinuria, and hypertension are main symptoms. Clinical findings and laboratory studies are necessary components of the workup, but advanced genetic and molecular methods must confirm sickle cell disease as the underlying cause.


Presentation

Sickle cell disease (SCD), globally regarded as one of the most prevalent hereditary diseases of the hematologic system, stems from mutations of genes (inherited through an autosomal recessive pattern) responsible for the formation of hemoglobin, specifically the β-globin chain [1] [2]. Depending on the phenotype, the medical entity may have a very poor prognosis in homozygous forms, whereas compound heterozygotes, as well as the heterozygotes, carry a slightly better life expectancy with less severe clinical manifestations [1]. The pathogenesis of SCD is centered around the defective hemoglobin molecules, which bind together in the circulation causing obstruction of the blood flow, sludging, and increased blood viscosity [3] [4]. As a result, ischemia and hypoxia of many tissues may arise. Renal failure, occurring on the grounds of microvascular obstruction, medullary fibrosis, focal segmental glomerulosclerosis (FSGS), and papillary necrosis, is known as sickle cell nephropathy (SCN), affecting up to 18% of all SCD cases [3] [4] [5]. Signs of SCN can start as early as infancy, when the capacity for urine concentration is diminished, resulting in polyuria and dehydration [3] [5] [6] [7]. In addition, microalbuminuria and proteinuria, as well as hematuria, anemia, and hypertension are main symptoms of SCN [3] [5] [6] [7]. In virtually all patients, progressive deterioration of glomerular filtration rate (GFR) increases the risk of acute kidney injury (AKI), chronic kidney disease (CKD, seen in up to 39% of SCD cases), and end-stage renal disease (ESRD) [1] [3] [5] [6] [8].

Polydipsia
  • In this case the diagnosis is irreversible nephrogenic diabetes insipidus, whose most common clinical manifestations are nocturia, polyuria, and polydipsia. 2. Distal tubular acidosis.[revistanefrologia.com]
Neglect
  • Retarding progression of chronic renal disease; the neglected issue of residual proteinuria. Kidney Int 2003;63:2254-61. 9. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al.[sjmms.net]
Nocturia
  • […] negative renal failure increased mortality risk for those with renal failure, regardless of treatment prognosis is 1 year for renal medullary carcinoma commonly very aggressive and metastasizes early Presentation Symptoms vaso-occlusion nausea vomiting nocturia[medbullets.com]
  • Improving nocturia has been reported to be an additional beneficial effect of ACEIs, presumably as a result of reduction in GFR.[emedicine.medscape.com]
  • HyposthenuriaHyposthenuria 1st clinical evidence of defective medullary1st clinical evidence of defective medullary tonicitytonicity Output 2000ml/day, nocturia andOutput 2000ml/day, nocturia and enuresisenuresis Max concentrating ability falls toMax[slideshare.net]
  • In this case the diagnosis is irreversible nephrogenic diabetes insipidus, whose most common clinical manifestations are nocturia, polyuria, and polydipsia. 2. Distal tubular acidosis.[revistanefrologia.com]

Workup

The diagnosis of sickle cell nephropathy can be made through a comprehensive clinical approach and subsequent laboratory testing. After collection of anamnestic data, during which findings such as hematuria and polyuria (and weakness due to dehydration and anemia) are noticed, urinalysis and additional imaging studies need to be performed. Urine dipstick testing is a useful initial tool to detect proteinuria and more detailed exams that assess the extent of protein loss are mandatory [3]. Further urinalysis reveals hematuria, in which case ultrasonography of the kidneys and the urinary bladder, cystoscopy, or urography, might be necessary to exclude other diagnoses (eg. the presence of stones or other lesions ) [2] [6]. Hyperechogenic renal pyramids and clubbing of the renal calyces are highly suggestive of SCN on ultrasonography and urography, respectively [5]. Serum creatinine and blood urea nitrogen (BUN) are important components of the workup, mainly in order to calculate the GFR and establish the severity of kidney disease. Erythropoietin (EPO) levels are markedly reduced in patients with sickle cell nephropathy, particularly in severe stages of renal failure [6]. To identify SCD as the underlying etiology of nephropathy, the aberrant hemoglobin (HbS) must be recognized through procedures such as isoelectric focusing (IEF), genetic studies, or high-performance liquid chromatography [2].

Penicillium
  • The pathogenesis is poorly understood, hence the retention of the title nephropathy. mycotoxic nephropathy caused by mycotoxins, such as ochratoxin and citrinin, produced by Penicillium and Aspergillus spp. reflux nephropathy pyelonephritis in which the[medical-dictionary.thefreedictionary.com]

Treatment

  • Further studies are needed to identify an accurate model and effective treatments for sickle cell nephropathy.[ncbi.nlm.nih.gov]
  • HMOX1 rs743811 associated with chronic kidney disease stage (OR 3.0, P 0.0001) in the University of Illinois cohort and end-stage renal disease (OR 10.0, P 0.0003) in the Walk-Treatment of Pulmonary Hypertension and Sickle cell Disease with Sildenafil[ncbi.nlm.nih.gov]
  • We outline the evidence for various treatment options and discuss others for which little evidence currently exists. 2011 Blackwell Publishing Ltd.[ncbi.nlm.nih.gov]
  • This article highlights the aspects of sickle cell nephropathy pathophysiology and clinical manifestations and describes the most recent advances in the diagnosis and treatment of this disorder.[ncbi.nlm.nih.gov]
  • Our goal is to find news treatment for this potentially devastating condition.[grantome.com]

Prognosis

  • Depending on the phenotype, the medical entity may have a very poor prognosis in homozygous forms, whereas compound heterozygotes, as well as the heterozygotes, carry a slightly better life expectancy with less severe clinical manifestations.[symptoma.com]
  • […] prognostic variable negative renal failure increased mortality risk for those with renal failure, regardless of treatment prognosis is 1 year for renal medullary carcinoma commonly very aggressive and metastasizes early Presentation Symptoms vaso-occlusion[medbullets.com]
  • […] nephropathy, the hyperfiltration is not associated with hypertension, as patients with SCN have lower systemic vascular resistance. [16] Nephrotic syndrome, though uncommon (up to 4% of patients with proteinuria) is associated with a very poor renal prognosis[ncbi.nlm.nih.gov]
  • Conclusion DPLN with SCN is a rare entity with poor prognosis, which may be overlooked and needs aggressive management.[diagnosticpathology.biomedcentral.com]
  • Renal medullary carcinoma, abbreviated RMC, is a rare malignant kidney tumour associated with sickle cell trait and a poor prognosis. General Rare. Usually young adults.[librepathology.org]

Etiology

  • To identify SCD as the underlying etiology of nephropathy, the aberrant hemoglobin (HbS) must be recognized through procedures such as isoelectric focusing (IEF), genetic studies, or high-performance liquid chromatography.[symptoma.com]
  • […] glomerulonhephritis,Focal segmental glomerulosclerosis (FSGS) and Membranous glomerulopathy Chronic tubulointerstitial nephropathy (CTIN) 6 A retrospective study cohort in king fahad hospital in KSA 2004 among 203 pt (11 with SCD, and 192 with ESRD due to diverse etiologies[slideplayer.com]
  • , pulmonary hypertension, sickle hepatopathy, and sickle cell nephropathy (SCN). [2] The primary cause of death in younger patients is usually infection; whereas, in older patients, the primary cause of death is mostly irreversible organ damage. [3] Etiology[ncbi.nlm.nih.gov]
  • Analgesic abuse also plays an important etiologic role and is usually seen in patients old enough to self-medicate.[njcponline.com]

Epidemiology

  • New chapters on glomerulonephritis associated with complement disorders, interventional treatments for hypertension, renal disease and cancer, and epidemiology and prognostic impact of acute kidney injury.[books.google.com]
  • Introduction Clinical definition nephropathy associated with sickle cell disease or trait vaso-occlusion renal medullary carcinoma Epidemiology incidence proteinuria 20-25% in sickle cell disease renal insufficiency 5-30% in sickle cell disease risk factors[medbullets.com]
  • Epidemiology The high prevalence of SCD in West Africa and parts of Asia represents a probable survival advantage because the presence of the sickle cell gene protects against malaria.[ncbi.nlm.nih.gov]
  • This can happen by continuing to demand and generate the best epidemiologic and medical evidence, and by always clearly communicating the magnitude of the risk of adverse effects of sickle cell trait.[hematology.org]
  • Epidemiology contd…Epidemiology contd… Clinical heterogenity inClinical heterogenity in manifestations is due to:manifestations is due to: Fetal Hb levelsFetal Hb levels 2,3-DPG levels2,3-DPG levels Linked mutationsLinked mutations ββs-haplotypess-haplotypes[slideshare.net]
Sex distribution
Age distribution

Pathophysiology

  • This review explores the pathophysiology and clinical manifestations of sickle cell nephropathy (SCN) and discusses how each complication can be investigated, monitored and managed in the outpatient setting.[ncbi.nlm.nih.gov]
  • This article highlights the aspects of sickle cell nephropathy pathophysiology and clinical manifestations and describes the most recent advances in the diagnosis and treatment of this disorder.[ncbi.nlm.nih.gov]
  • Assessment of conjunctival microvascular hemodynamics may improve our understanding of the pathophysiology and clinical management of sickle cell nephropathy.[ncbi.nlm.nih.gov]
  • This unique pathophysiologic alteration of the countercurrent mechanism suggests that the defect is due to an abnormality in trapping of solute in the renal papilla.[annals.org]
  • Sickle cell gene prevalence is about 8% in African Americans and about 25% in adult Nigerians. [5] Pathophysiology HbS polymerization is the key pathophysiological event, and it occurs during cellular or tissue hypoxia, oxidative stress, or dehydration[ncbi.nlm.nih.gov]

Prevention

  • Preventing or slowing the nephropathy can improve the outcome of this complication of the devastating sickle cell disease.[ncbi.nlm.nih.gov]
  • What can I do to help prevent problems? Get regular check ups in the Comprehensive Sickle Cell Clinic so that any problems can be picked up early and treated to prevent worsening problems.[chkd.org]
  • This may allow us to design strategies to treat or prevent certain complications of the disease.[grantome.com]
  • Emphasis has been given to the description of the measures taken in order to prevent and minimize the deleterious effects of sickling in the peri-transplantation period. top of page[minervamedica.it]
  • Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. ‏[books.google.com]

References

Article

  1. Nath KA, Hebbel RP. Sickle cell disease: renal manifestations and mechanisms. Nat Rev Nephrol. 2015;11(3):161-171.
  2. Bender MA, Douthitt Seibel G. Sickle Cell Disease. 2003 Sep 15 [Updated 2014 Oct 23]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  3. Saborio P, Scheinman JI. Sickle cell nephropathy. J Am Soc Nephrol. 1999;10(1):187-192.
  4. Lonergan GJ, Cline DB, Abbondanzo SL. Sickle cell anemia. Radiographics. 2001;21(4):971-994.
  5. Pham PT, Pham PC, Wilkinson AH, Lew SQ. Renal abnormalities in sickle cell disease. Kidney Int. 2000;57(1):1-8.
  6. Ataga KI, Orringer EP. Renal abnormalities in sickle cell disease. Am J Hematol. 2000;63(4):205-211.
  7. Alhwiesh A. An update on sickle cell nephropathy. Saudi J Kidney Dis Transpl. 2014;25(2):249-265.
  8. Ephraim RKD, Osakunor DNM, Cudjoe O, et al. Chronic kidney disease is common in sickle cell disease: a cross-sectional study in the Tema Metropolis, Ghana. BMC Nephrol. 2015;16:75.

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Last updated: 2019-07-11 20:43