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].

• Anemia

  An infection with human parvovirus B19 (HPV B19), is a rare cause of acute nephrotic syndrome with severe hemolysis and life-threatening anemia. [ncbi.nlm.nih.gov]

  Itano HA, Keitel HG, Thompson D (1956) Hyposthenuria in sickle cell anemia: a reversible renal defect. [link.springer.com]

  Overview Sickle cell anemia is an inherited form of anemia — a condition in which there aren't enough healthy red blood cells to carry adequate oxygen throughout your body. [mayoclinic.org]

  […] of sickle-shaped red blood cells and anemia. [icd10data.com]

  In addition, microalbuminuria and proteinuria, as well as hematuria, anemia, and hypertension are main symptoms of SCN. [symptoma.com]

• Weakness

  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. [symptoma.com]

  If you notice one-sided paralysis or weakness in the face, arms or legs; confusion; trouble walking or talking; sudden vision problems or unexplained numbness; or a headache, call 911 or your local emergency number right away. [mayoclinic.org]

  Unlike in Caucasians, the African populations exhibited weak LD and formed two small LD blocks. In East Asian populations (CHB, CHD and JPT) and south Asian populations (GIH), the LD is fragmented (Fig. S1). [journals.viamedica.pl]

• 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]

• Hypertension

  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]

  In addition, microalbuminuria and proteinuria, as well as hematuria, anemia, and hypertension are main symptoms of SCN. [symptoma.com]

  Phone: 617-636-7429 Fax #: 617-636-0066 Hematuria, proteinuria, hypertension, renal insufficiency, kidney stones, fluid and electrolyte imbalance View Full Profile Lawrence S. [floatinghospital.org]

  Gordeuk VR, Sachdev V, Taylor JG, Gladwin MT, Kato G, Castro OL (2008) Relative systemic hypertension in patients with sickle cell disease is associated with risk of pulmonary hypertension and renal insufficiency. [link.springer.com]

• Short Arm

  The β-globin gene is found on the short arm of chromosome 11 3 Autosomal recessive 4 Sickle cell distribution 5 Post infectious glomerulonephritis (IGN) Chronic glomerulonhephritis,Focal segmental glomerulosclerosis (FSGS) and Membranous glomerulopathy [slideplayer.com]

  Deletions in short arm segment 11p15 have been described in other neoplasms like hereditary and spontaneous cases of Wilms' tumor, rhabdomyosarcoma and bladder and breast cancer. The Hp segment is thought to contain a suppressor gene. [indianjurol.com]

• Suggestibility

  Our study suggests that sickle cell disease produces similar lesions in patients with sickle cell nephropathy. [ncbi.nlm.nih.gov]

  There is, therefore, compelling evidence to suggest that HU administration can modify renal parameters in SCD patients. [academic.oup.com]

  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]

• Hematuria

  In addition, microalbuminuria and proteinuria, as well as hematuria, anemia, and hypertension are main symptoms of SCN. [symptoma.com]

  Acute gross hematuria or persistent microscopic hematuria. Without RBC casts or dysmorphic (other than sickle) RBCs. Ultrasound or helical computed tomography (CT) shows distinctive medullary abnormalities. [accessmedicine.mhmedical.com]

  Snapshot An 18-year-old African American man with a history of sickle cell trait presents with 1 week of painless gross hematuria. On review of systems, he endorses a 10 pound weight loss within the past 2 months. [medbullets.com]

  Recurrent hematuria. Proteinuria. renal papillary necrosis. [slideplayer.com]

• Polyuria

  Signs of SCN can start as early as infancy, when the capacity for urine concentration is diminished, resulting in polyuria and dehydration. [symptoma.com]

  Beginning in childhood, patients with SCD develop a urinary concentrating defect resulting in polyuria and a predisposition to nocturnal enuresis and dehydration. [ncbi.nlm.nih.gov]

  […] 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 polyuria [medbullets.com]

  […] principal cells by inhibiting water channel delivery and, over a prolonged period of time, by suppressing channel production. [2, 11, 12] A minority of reports, however, propose that lithium-induced partial central diabetes insipidus may play a role in the polyuria [emedicine.medscape.com]

• Kidney Failure

  This medicine helps protect the kidney and decrease proteinuria. The kidney doctor may suggest a change in diet to help prevent worsening of the damage. End stage kidney failure is treated with dialysis. [chkd.org]

  Sickle cell nephropathy is a common complication of sickle cell disease that affects both children and adults, and may lead to kidney failure. The mechanisms that cause kidney damage in sickle cell disease are not well understood. [grantome.com]

  Acute kidney injury - acute kidney failure usually occurs when the blood supply to the kidneys is suddenly interrupted or when the kidney becomes overloaded with toxins. [sicklecell-ourvoice.blogspot.com]

  Majority of patients with sickle cell disease and kidney failure present between the ages of 20 and 40 years and these patients often are dead within 4 years of diagnosis of kidney failure 2,4. [kidneysolutions.wordpress.com]

  Sickle cell nephropathy (SCN) is a progressive complication of sickle cell disease (SCD) that begins in childhood and results in renal (kidney) failure and early mortality in nearly 12% of adults with hemoglobin SS (HbSS). [clinicaltrials.gov]

• Renal Injury

  In these cohorts of children and adults, we will study the effect of treatment on parameters of renal dysfunction and whether certain biomarkers of renal injury improve with treatment of the disease. [grantome.com]

  Keywords: Albumin/creatinine ratio, Cr Cl, ESRD, hemoglobin, renal insufficiency, SCA How to cite this article: Abdul-Rahman IS. Urine Albumin/creatinine ratio: A reliable marker of renal injury in sickle cell nephropathy. [sjmms.net]

  Urinary microalbumin levels are considered to be one of the early renal injury markers in patients with sickle cell disease. Testing for it is non-invasive, readily available, and easy to perform in most of the clinical settings. [journal.frontiersin.org]

  Renal abnormalities would include: hematuria renal papillary necrosis tubular dysfunction proteinuria nephrotic syndrome chronic kidney disease renal medullary carcinoma acute kidney injury pyelonephritis Hematuria and renal papillary necrosis in sickle [renalandurologynews.com]

  The underlying mechanisms of renal injury or sickle cell nephropathy (SCN) relate mainly to hypoxia and ischemia. The clinical manifestations are determined by the predominant site of tubular involvement. [emedicine.medscape.com]

• 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]

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].

• Microalbuminuria

  Logistic regression was used to calculate the ORs for microalbuminuria after controlling for multiple covariates simultaneously. [sjmms.net]

  Aloni et al. showed, by bivariate analysis, that age was the main determinant of microalbuminuria in children with SCD [ 7 ]. [academic.oup.com]

  McKie KT, Hanevold CD, Hernandez C, Waller JL, Ortiz L, McKie KM (2007) Prevalence, prevention, and treatment of microalbuminuria and proteinuria in children with sickle cell disease. [link.springer.com]

  For clinical practice, microalbuminuria (MA) was defined as Urine MA of ≥20 mg/L ( 14 ). [journal.frontiersin.org]

  Patients with SCN advance through stages of tubular dysfunction and hyperfiltration, microalbuminuria through heavy proteinuria, and ultimately loss of GFR. [ncbi.nlm.nih.gov]

Further studies are needed to identify an accurate model and effective treatments for sickle cell nephropathy. [ncbi.nlm.nih.gov]

Our goal is to find news treatment for this potentially devastating condition. [grantome.com]

Curr Opin Hematol 2012 ; 19 : 149 – 155 36 Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med 2008 ; 358 : 1362 – 1369 37 et al. Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia. [academic.oup.com]

[…] renal medulla is low enough to induce RBC sickling sickling of red blood cells in medulla capillaries cause increased viscosity increased viscosity causes ischemia and infarction in renal medulla this can lead to renal infarcts and papillary necrosis Prognosis [medbullets.com]

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]

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]

[…] 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]

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]

Analgesic abuse also plays an important etiologic role and is usually seen in patients old enough to self-medicate. [njcponline.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]

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]

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]

Although the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is thought to be the best equation, overestimation of as much as 45 mL/min has been observed. [21] Limited studies suggest that cystatin C–based equations may enable clinicians [emedicine.medscape.com]

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 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]

Albuminuria is a commonly used biomarker of glomerular damage; however the correlations of albuminuria with specific measurements of glomerular function and pathophysiology have not been determined. [clinicaltrials.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]

Preventing or slowing the nephropathy can improve the outcome of this complication of the devastating sickle cell disease. [ncbi.nlm.nih.gov]

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]

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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.