Renal Lesions in Sickle Cell Nephropathy in Children

Tejani, Amir; Phadke, Kishore; Adamson, Orlando; Nicastri, Anthony D.; Chen, C.K.; Sen, Debashis

doi:10.1159/000183404

Cited by 78 publications

(33 citation statements)

References 7 publications

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“…19,20 Previous studies have shown similarities in the severity of renal structural and functional changes in SS mice compared with humans with sickle cell disease, including early nephromegaly, glomerular hypertrophy, cortical fibrosis with cyst formation, chronic interstitial nephritis, renal tubular siderosis, and concentrating defects. 4,[21][22][23][24][25] Further studies will be required to establish whether the glomerular lesions are identical to the mesangioproliferative glomerulopathy found in sickle cell disease patients. In this study, several important dissimilarities were noted, including the absence of papillary necrosis and more severe injury to the renal cortex in SS mice than in humans with sickle cell disease.…”

Section: Discussionmentioning

confidence: 99%

Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease

Manci

Hillery

Bodian

et al. 2006

Blood

123

155

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Because Berkeley sickle cell mice are used as an animal model for human sickle cell disease, we investigated the progression of the histopathology in these animals over 6 months and compared these findings to those published in humans with sickle cell disease. The murine study groups were composed of wild-type mixed C57Bl/6-SV129 (control) mice and sickle cell (SS) mice (␣ ؊/؊ , ␤ ؊/؊ , transgene ؉) of both sexes and between 1 and 6 months of age. SS mice were similar to humans with sickle cell disease in having erythrocytic sickling, vascular ectasia, intravascular hemolysis, exuberant hematopoiesis, cardiomegaly, glomerulosclerosis, visceral congestion, hemorrhages, multiorgan infarcts, pyknotic neurons, and progressive siderosis. Cerebral perfusion studies demonstrated increased blood-brain barrier permeability in SS mice. SS mice differed from humans with sickle cell disease in having splenomegaly, splenic hematopoiesis, more severe hepatic infarcts, less severe pulmonary manifestations, no significant vascular intimal hyperplasia, and only a trend toward vascular medial hypertrophy. Early retinal degeneration caused by a homozygous mutation (rd1) independent from that causing sickle hemoglobin was an incidental finding in some Berkeley mice. While our study reinforces the fundamental strength of this model, the notable differences warrant careful consideration when drawing parallels to human sickle cell disease. (Blood. 2006;107: 1651-1658)

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Section: Discussionmentioning

confidence: 99%

Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease

Manci

Hillery

Bodian

et al. 2006

Blood

123

155

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“…The fact that small-molecular-weight proteinuria was found in most of the patients is another set of data against the glomerular involvement. Glomerular diseases have been found in autopsy of patients with thalassemia and have been reported to lead to end-stage renal disease in some [7, 11]. Etiologies such as repeated infection, inability to clear the immune complexes caused by infection and repeated use of desferroxamine have been postulated [7, 9, 30].…”

Section: Discussionmentioning

confidence: 99%

“…Renal involvement has been extensively studied in both Cooley’s disease and sickle cell anemia [1, 2, 3, 4, 5, 6, 7, 8] but sparingly in β-thalassemia/Hb E disease [9, 10]. There are several factors that may adversely affect the kidney in thalassemia: chronic anemia, iron overload, hemosiderosis and oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Renal Function in Adult Beta-Thalassemia/Hb E Disease

Ong-Ajyooth¹,

Malasit²,

Ong-Ajyooth³

et al. 1998

Nephron

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β-Thalassemia hemoglobin E (β-thal/Hb E) is the commonest form of hemoglobinopathy in Thailand. Shortened red cell life span, rapid iron turnover and tissue deposition of excess iron are major factors responsible for functional and physiological abnormalities found in various forms of thalassemia. Increased deposition of iron had been found in renal parenchyma of thalassemic patients, but no systematic study of the effect of the deposits on renal functions has been available. The purpose of this study is to describe the functional abnormalities of the kidney in patients with β-thal/Hb E and provide evidence that increased oxidative stress might be one of the factors responsible for the damage. Urine and serum samples from 95 patients with β-thal/Hb E were studied comparing with 27 age-matched healthy controls. No difference in the creatinine clearance was observed. β-thal/Hb E patients excreted significantly more urinary protein (0.8 ± 0.5 vs. 0.3±0.1 g/day, p < 0.001). Aminoaciduria was found in 16% of the patients. Analysis of urinary protein by SDS-PAGE electrophoresis and silver staining revealed abnormal pattern of protein with increased small molecular weight (<45 kD) bands. Morning urine analysis showed significant lower urine osmolality (578.3 ± 164.6 vs. 762.4 ± 169.9 mosm/kg, p < 0.001) in patients. Patients excreted more NAG (N-acetyl beta-D-glucosaminidase, 26.3 ± 41.3 vs. 8.4 ± 3.9 U/g Cr, p < 0.0001) and β₂-microglobulin, 124.3 ± 167 vs. 71 ± 65.5 µg/g Cr, p = 0.001. Plasma and urine MDA (malonyldialdehyde) levels were both raised (p < 0.0001). Nine patients were selected for renal acidification study. All were found to be normal, but showed poor response to DDAVP challenge (urine osmolality 533 ± 71). This is the first report of renal tubular defects found associated with β-thal/Hb E disease. The mechanism leading to the damage is not known but it might be related to increased oxidative stress secondary to tissue deposition of iron, as indicated by the raised levels of serum and urine MDA. It is not known whether these functional defects would have any long-term effects on the patients. Further studies are warranted and means of prevention of these defects should urgently be sought.

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“…1 Many factors could play an important role in the pathogenesis of the disease. It has been shown that 25% of patients with sickle cell disease have proteinuria and the glomerular capillary hypertension may be a pathogenic factor in sickle cell nephropathy.…”

Section: Ahmed Mukhtarmentioning

confidence: 99%

Immunolocalization of MP84 in renal biopsy sections of sickle cell nephropathy patients

Mukhtar¹

1998

Sao Paulo Med. J.

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Renal Lesions in Sickle Cell Nephropathy in Children

Cited by 78 publications

References 7 publications

Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease

Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease

Renal Function in Adult Beta-Thalassemia/Hb E Disease

Immunolocalization of MP84 in renal biopsy sections of sickle cell nephropathy patients

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