SCD is one of the most frequent hereditary haematologic diseases in the world. kidney is involved in SCD.

1. Sickle cell disease renal manifestations
Dr m.s forghani MD, MUK

2. Overview of SCD
• SCD is one of the most frequent hereditary haematologic diseases in the
world.
• Its most severe and common form, sickle cell anaemia (SCA), results from
homozygosity for the mutant form of the gene that encodes globin.β‑
• SCA is also the most severe form of SCD in terms of its renal
manifestations.
• there are 5 variants of SCD that known as Cameroon, Senegal, Benin,
Bantu, and Saudi-Asian.
• Their clinical importance is because some are associated with higher
HbF levels, e.g., Senegal and Saudi-Asian variants, and tend to have
milder disease.
• These renal manifestations are generally less severe in the double
heterozygous forms and SCT

3. pathobiology of sickle cell disease
In kidney medulla Hb S polymerization
is governed by low PH , low PO2, high Osmolality
Abnormal S-RBC membrane
Adhesion receptor
Vasa recta Low blood flow
increase RBC adhesion
to the endothelium

4. Renal vasculopathy in SCD

5. Glomerular hyperfiltration
• This finding indicates that (Increase RPF, RBF,GFR)
glomerular hyperfiltration is driven by increased
glomerular perfusion and increased effective
glomerular filtration surface area, but not by increased
glomerular capillary hydrostatic pressure.
• The investigators found significantly increased GFR
and renal plasma flow in patients with sickle cell
disease versus controls, with a decrease in filtration
fraction (FF), which suggests predominant dilatation
of the efferent arteriole and loss of juxtamedullary
nephrons

6. Acute kidney injury
• AKI occurs in 4–10% of hospitalized patients
with SCD, and is more frequent in patients with
acute chest syndrome (13.6%) than in
patients with painful crisis (2.3%).
• AKI is prognostically important in SCD, as
it predicts a less favourable outcome among
patients who are transferred to the intensive
care unit.

7. Pathogenesis of SCN
Increased renal growth
Increased Na delivery, Na reabsorption, increased PCT metabolic function
(renal enlargement)
Glomerular and other histologic lesions
Capillary congestion, mesangial proliferation, glomerulosclerosis, interstitial
nephritis and fibrosis
Proteinuria
27% of patients in the first three decades, nephrotic syndrome in 4%,
Albuminuria levels >500 mg/g creatinine are associated with progressive
CKD
Chronic kidney disease: 29-42%
vascular, endothelial, tubular, interstitial process interactions
CKD risk factors: PB19, HTN,Hb level, age, PAH

8. Renal manifestations of sickle cell disease
Haemodynamic glomerular injury
 Endothelium–podocyte/pericyte crosstalk
 Haemolysis-induced renal injury
 Urinary concentration defect
 Hematuria
 Distal nephron dysfunction
 Podocyte integrityis critically dependent upon a healthy glomerular endothelium
 Podocyte : VEGF ---> NO
 SFLT1 => Inhibit trophic effect of VEGF on podocyte
 Endothelium : ET-1, TNF => induced podocyte dysfunction and proteinuria
 Endothelial dysfunction: induced procuagolant, poinflammatory phenotype and
might perturb the behaviour of pericytes
 increases wall tension , Increased wall tension might damage the
glomerular endothelium, the podocyte, and the filtration barrier, areas
of the glomerular basement membrane will be bereft of podocyte foot
processes => FSGS

9. Haemolysis-induced renal injury
• HbS is an unstable protein that undergoes autoxidation and
denaturation to produce oxidants and free haem
• Epithelial IRON accumulation
• Heme triggers TLR4 (mesangial, endothelial, epithelial,
podocyte) signaling leading to endothelial cell activation
( proinflammatory and progoagulant phenotype)
• free haem and Hb S: promotes proliferation of smooth
muscle cells , proinflammatory and profibrogenic gens
upregulation in tubulointerstitial and glomerular compartment

10. Urinary concentration defect& Hematuria
Partial Distal RTA in 40% case of SCD

11. Treatment: Hematuria
Hematuria:
• is a common complication of SCN and often self limited in
nature. Conservative measures such as bed rest, to prevent
dislodging of blood clots, and oral hydration are the
preferred treatments.
• Severe cases have been treated with urine alkalinization, to
increase urine flow, and blood transfusion to reduce the
hemoglobin S concentration.

12. Treatment: Proteinuria
• Proteinuria and hypertension should be controlled
• A patient with proteinuria should be started on ACE
inhibitor or ARB, as it can reduce protein excretion by as
much as 50%.
• The blood pressure goal in a patient with proteinuria is less
than 130/80mmHg.
• In SCD patient should avoid the use of diuretics as they
can contribute to intravascular volume depletion and cause a
sickling crisis.
• The addition of hydroxyurea to ACE inhibitoror ARB
therapy might aid in reduction of proteinuria as well.
• NSAIDs should also be avoided as they can reduce the
renal blood flow and depress the GFR.

13. Treatment : Anemia
• Treatment of anemia is common in all chronic kidney disease
patients; however, those with SCD have a lower goal
hemoglobin level.
• Recommendations are to keep hemoglobin levels no higher
than10g/dL an davoid a hematocrit rise of greater than 1–
2% per week. Higher levels of hemoglobin can precipitate a
vasoocclusive crisis.
• Sickle cell patients often require blood transfusions to
maintain this hemoglobin level.
• The use of erythropoietin is not routine in ESRD sickle cell
patients, as it does not have the benefit of increasing the
proportion of healthy hemoglobin A as a blood transfusion
does.

14. ESRD
• The incidence of dialysis-related complications is no
higher in SCD patients than in other ESRD patients.
• After 2 years of hemodialysis, SCD patients and non SCD
patients have “similar rates of mortality”
(33%vs.37%,respectively).
• However, patients with and without SCD on hemodialysis
showed decreased “survival rates” in the SCD
patients at both 3 years and 5 years
(60%vs.80%at3yearsand40%vs.60%at5years).

15. Kidney transplantation
• The 1-year acute rejection rate and graft survival seen in SCD
patients were not significantly different from those receiving kidney
transplant for other causes of renal failure.
• However, the 3-year rates did show a decline in graft survival in
sickle cell patients (48%vs.60% when compared with ethnically
matched kidney recipients).
• The overall survival is also lower than the general population at
both 1 year (78%vs.90%) and 3 years (59%vs.81%).
• Some authors have noted an increase in the frequency of painful
sickle cell crisis after transplantation likely due to the subsequent
rise in hemoglobin post-transplant.