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.
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  . 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 . 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  . 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   . Signs of SCN can start as early as infancy, when the capacity for urine concentration is diminished, resulting in polyuria and dehydration    . In addition, microalbuminuria and proteinuria, as well as hematuria, anemia, and hypertension are main symptoms of SCN    . 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)     .
- 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]
[…] 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]
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]
Improving nocturia has been reported to be an additional beneficial effect of ACEIs, presumably as a result of reduction in GFR. [emedicine.medscape.com]
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 . 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 )  . Hyperechogenic renal pyramids and clubbing of the renal calyces are highly suggestive of SCN on ultrasonography and urography, respectively . 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 . 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 .
- Staphylococcus Aureus
aureus Osteomyelitis Uncommon Mycoplasma pneumonia Pneumonia Pleural effusions; multilobe involvement Chlamydia pneumonia Pneumonia Parvovirus B19 Bone marrow suppression (aplastic crisis) High fever common; rash and other organ involvement infrequent [slideshare.net]
Escherichia coli and other Gram-negative enteric pathogens Septicaemia, urinary tract infection, osteomyelitis Focus sometimes inapparent Staphylococcus aureus Osteomyelitis Uncommon Mycoplasma pneumonia Pneumonia Pleural effusions; multilobe involvement Chlamydia [slideshare.net]
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]
Treatment The majority of tubular abnormalities in SCD patients do not require treatment in addition to symptomatic treatment in pathological situations leading to dehydration or volume overload, according to the predominant functional abnormality. [revistanefrologia.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.  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).  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.  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.  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]
The potential for prevention and reversal of kidney damage in SCD is not known. [clinicaltrials.gov]
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