Renal abnormalities in sickle cell disease

Abstract

Renal abnormalities in sickle cell disease. Sickle cell nephropathy is indicated by sickled erythrocytes, with the consequent effects of decreased medullary blood flow, ischemia, microinfarct and papillary necrosis. Impaired urinary concentrating ability, renal acidification, hematuria, and potassium secretion are also found. There may be a causal relationship between an increase in nitric oxide synthesis and experimental sickle cell nephropathy, and some studies have indicated that the progression of sickle cell nephropathy is hemodynamically mediated. Although there are many studies showing that proteinuria, nephrotic syndrome, chronic progressive renal failure, and acute renal failure syndromes are the outcome of this disease, the pathogenic mechanism(s) and potential therapies remain to be elucidated. Survival of patients with sickle cell nephropathy who progress to end-stage renal disease (ESRD) is equal to non-diabetic ESRD patients, and graft survival rates are also similar for those who undergo renal transplantation. This article presents a historical review of the glomerular and tubular disorders associated with sickle cell nephropathy, and reviews therapeutic indications to slow its progression. Further research is needed.

Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B

“…Renal complications are a well known cause of morbidity and mortality in sickle cell disease, and the incidence of renal failure increases as overall patient survival improves [1][2][3][4][5][6][7][8][9][10]. Early elements of sickle cell renal disease include increased renal plasma flow accompanied by glomerular hyperfiltration and increased proximal tubular function, as well as hematuria.…”

“…Early elements of sickle cell renal disease include increased renal plasma flow accompanied by glomerular hyperfiltration and increased proximal tubular function, as well as hematuria. Subsequently, reduced concentrating ability, proteinuria from focal segmental glomerulosclerosis, papillary necrosis, impaired urine acidification and potassium secretion, and reduced glomerular filtration may develop [reviewed in 1,5,11].…”

Nitric Oxide-dependent Generation of Reactive Species in Sickle Cell Disease

“…The intermittent vascular occlusion occurring in SCD 1 is characterized by acute, painful crises and leads to the renal and hepatic tissue injury and dysfunction manifested by patients with this hemoglobinopathy (1)(2)(3). Peripheral vascular insufficiency, accompanied by periodic restoration of blood flow, places ischemic organs at risk of additional injury by inducing a proinflammatory state reflected by enhanced superoxide (O 2 . )…”

Murine glutathione S‐transferase A1‐1 in sickle transgenic mice

“…The proposed process involves ischemia and microinfarction resulting from medullary hypoxia, acidosis, and hyperosmolarity, an environment that promotes red blood cell (RBC) sickling. Medullary insult leads to a urine-concentrating defect [10]; studies analyzing SCA patients demonstrate the inability of these patients to concentrate their urine, a likely irreversible effect after 15 years [11]. Glomerular hypertension and increased glomerular permeability ensue, ultimately resulting in proteinuria and renal insufficiency [12].…”