Sickle cell nephropathy. Clinical manifestations and new mechanisms involved in kidney injury.

Kidney problems are among the most common complications in sickle cell disease (SCD). They occur early in childhood and are one of the main factors related to mortality in these patients. The main underlying pathogenic mechanisms are vaso-occlusion and haemolysis. The renal medulla has ideal conditions for the sickling of red cells due to its low partial pressure of oxygen, high osmolarity and acidic pH. Initially, sickle-cell formation in the vasa recta of the renal medulla causes hyposthenuria. This is universal and appears in early childhood. Microscopic and macroscopic haematuria also occur, in part related to renal papillary necrosis when the infarcts are extensive. Release of prostaglandins in the renal medulla due to ischaemia leads to an increase in the glomerular filtration rate (GFR). Adaptively, sodium reabsorption in the proximal tubule increases, accompanied by increased creatinine secretion. Therefore, the GFR estimated from creatinine may be overestimated. Focal segmental glomerulosclerosis is the most common glomerular disease. Albuminuria is very common and reduction has been found in 72.8% of subjects treated with ACE inhibitors or ARB. Recent evidence suggests that free haemoglobin has harmful effects on podocytes, and may be a mechanism involved in impaired kidney function in these patients. These effects need to be better studied in SCD, as they could provide a therapeutic alternative in sickle cell nephropathy.