The kidney is susceptible to damage through several mechanisms which may work independently or in tandem. The disease process may effect glomerular and proximal tubular function as well as the urinary concentrating mechanism in the medulla. HbSS patients are generally the most severely affected, but significant pathology is also frequently observed in adults with HbSC, and even in carriers of SCD (See Chap.​ 1). A distal renal tubule concentrating defect is usually the first manifestation of renal damage, resulting in hyposthenuria (an inability to concentrate urine). Increased renal cortical blood flow due to anemia and high cardiac output is apparent from early childhood, and is associated with an increased glomerular filtration rate (GFR). Cortical and medullary ischaemia may also contribute to the increase in GFR. This glomerular hyperfiltration causes glomerular hypertrophy and is partly responsible for the progressive glomerular damage, which manifests initially as microalbuminuria and at later stages, proteinuria and progressive renal impairment. Histologically the glomeruli become enlarged and congested with sickled red cells, and there is proliferation of the mesangium (Fig. 8.1). Later on the changes of focal and segmental glomerulosclerosis (FSGS) may develop.

In the medulla, there is occlusion of the vasa recta, (the vessels involved in the counter-current urinary concentration mechanism), together with ischemic damage and fibrosis. These changes are probably due to enhanced sickling in medullary conditions of slow blood flow, hemoconcentration, acidosis and low oxygenation.

In adults over the age of 30 there tends to be a progressive drop in GFR, and the insidious development of renal failure.

Microalbuminuria is present in up to 21 % of children and over 60 % of adults. The prevalence of proteinuria is around 4 % of children, 10 % of teenagers, 20 % of young adults and over 40 % in adults over 40 years of age. Renal insufficiency is seen in over 21 % of adults and progresses to end stage renal failure in 4-12 % of patients. It is likely that as survival and life expectancy improve, renal disease will become more common.

Children who develop a concentrating defect pass large volumes of urine and often have problems with nocturnal enuresis, persisting into the teenage years. Adults may have nocturia, which can be associated with increasing proteinuria. Progressive loss of renal function occurs without noticeable symptoms and patients may present to clinic with end-stage renal failure.

Screening and risk management for renal disease should be part of the routine care for children and adults and we recommend that these are part of the annual review. The assessment should include blood pressure monitoring, measurement of creatinine and eGFR and quantification of proteinuria by albumin-creatinine or protein-creatinine ratio (See Chap. 19). Children or their carers should be questioned about enuresis, hematuria and urinary infections.

Creatinine levels are usually low in SCD and a trend of increase over time, even if still within the normal range, may indicate worsening renal function. Patients presenting with proteinuria or chronic renal dysfunction should have investigations to rule out alternative causes including autoimmune disorders, chronic viral infection and structural abnormalities in the renal tract (demonstrable by ultrasound).

These patients should be reviewed by a renal physician with an interest in SCD, preferably in a specialist sickle-renal clinic. Renal biopsy should be considered, particularly in those with an atypical presentation or features which may suggest an alternative diagnosis. Recommendations for treatment are shown in Table 8.1.