SCN had been reported to be far less frequent and severe in HbSC and HbAS than other phenotypes [4, 5]. Hyperfiltration assessed than by estimated GFR is found in only 5%, albuminuria in 7%, and chronic renal failure in 2% of young HbSC patients compared with 51%, 59%, and 7%, respectively, in SCA patients [5]. Sickle cell-associated glomerulopathy is also rarely encountered in HbSC patients. However, further data are needed to address the issue as to whether HbSC may be an additional risk factor for chronic kidney diseases from other causes, as recently suggested for patients with sickle cell trait [4]. Twenty-five to thirty percent of SCD patients were reported to have proteinuria, and 5�C18% of them develop renal failure [6, 7]. SCN constitute 0.

11% Inhibitors,Modulators,Libraries of ESRD reported in the United States renal data survey (USRDS); 93% of them were African American. SCD was documented as risk factor for Inhibitors,Modulators,Libraries development of ESRD [5]. The mean age of the patient was 23 to 40 years, and survival was found to be 4 years [3, 8, 9]. Several mechanisms had been Inhibitors,Modulators,Libraries proposed as cause of various Inhibitors,Modulators,Libraries glomerular and tubular changes in patients with SCN. These proposed mechanisms include glomerular and tubular ischaemia, iron overload and subsequent deposition in the kidneys, continued intracapillary fragmentation and phagocytosis of sickled red cells, immune complex formations, FSGS associated with glomerular hyperfiltration, and/or intrinsic glomerular capillary injury [10]. The pathophysiology of SCN (Figure 1) is related to the normal renal medullar environment which is characterised by low oxygen tension, low pH, and high osmolality.

These conditions in Inhibitors,Modulators,Libraries SCD patients predispose to red blood cell sickling, increased blood viscosity leading to ischemia, and eventual infarction of renal microcirculation. Glomerular ischemia leads to compensatory increase in renal blood flow and glomerular filtration rate (GFR). The resulting hyperfiltration, combined with glomerular hypertrophy, probably contributes to glomerulosclerosis. As glomerulosclerosis becomes more extensive, the GFR starts to decrease and nonselective proteinuria may result leading to chronic kidney disease and subsequently ESRD [11�C13]. Red blood cell (RBC) sickling in the vasa rectae is believed to interfere with the countercurrent exchange mechanism in the inner medulla. The resulting impairment of free water resorption manifests clinically as nocturia or polyuria [14, 15].

Figure 1 Schematic diagram of pathophysiology of SCN. Furthermore, ischemia involving the renal medulla will also lead to the inability to maintain a hydrogen ion gradient (causing an incomplete form of distal renal tubular acidosis) and an electrochemical gradient (leading to hyperkalemia) along the collecting ducts. Gross hematuria can be Anacetrapib secondary to papillary necrosis resulting from medullary ischemia and infarction.