Sickle cell nephropathy (SCN) is a condition characterized by kidney damage due to sickled erythrocytes, affecting 60% of patients with sickle cell disease and leading to complications like end-stage renal disease in a significant percentage. Clinical manifestations include hemolysis, vaso-occlusion, and various renal dysfunctions such as hyperfiltration, proteinuria, and acute kidney injury. Diagnosis focuses on clinical presentation and exclusion of other conditions, while management may involve ACE inhibitors, hydration, and addressing complications such as infection and electrolyte imbalances.

1. Dr. Mohamed Abbass
Consultant Nephrology
PGDD,CARDIFF,UK
Nephro-Medical Tube

2. Definition and introducation
 Sickle cell nephropathy (SCN) is presence of
sickled erythrocytes in the renal medulla that
result in decreased medullary blood flow,
ischemia, microinfarcts and papillary necrosis in
the kidneys
 The renal medulla chractrized by lower oxygen
tension, high osmolarity, lower pH, and relatively
sluggish blood flow, is a good environment for
“sickling” and microvascular obstruction.

3.  Renal involvement represent 60% of patients
with HbSS but 10 – 15% of these patients will
develop ESRD.
 HbSA patient may develop tubular defects later
in life, and no risk of CKD.
 SCN = different renal lesions that affect the
glomerulus and tubulointerstitium.
 Glomerular hyperfiltration and glomerulomegaly
is evident even in patients without clinical
disease.

4. Pathogenesis and clinical manifestations
 Hemolysis, vasoocclusion, and ischemia
reperfusion are the clinical hallmarks of SCD
 Onset typically occurs after age 30, with 50%
progressing to ESRD within 2 years and death
within 4 years despite dialysis.

5.  Hyposthenuria (Concentration defect) due to
repeated infarction and urinary papillary necrosis 
Progresses with age
 Metabolic acidosis (type 4 RTA) (Acidification
defect) due to defects in (H+) ion excretion
 Hyperuricemia (impaired urate clearance) due to
ischemic injury of the distal tubules  Progresses
with age

6.  Hyperphosphatemia due to increase tubular
reabsorption of phosphate also Hypernatremia
due to increased sodium reabsorption conjugated
with phosphate reabsorption.
 Hyperkalemia due to depression of renin 
Hyporeninemic hypoaldosteronism and impairment
of potassium excretion due to ischemic injury of the
collecting ducts

7.  Hyperfiltration {increased GFR (>50%) } due to
vasodilatation as compensatory response to chronic
hypoxia in renal medulla , which lead to
albuminuria/proteinuria, sickle glomerulopathy in
early stage then CKD later
 Decreased RBF due to congestion of capillary loops
with sickled cells and hemosiderin; inflammatory
vasoactive substances

8.  Glomerular abnormalities and proteinuria
due to glomerular hyperfiltration; cytokines and
iron overload, then FSGS/MPGN may be develop
especially in massive proteinuria
 Renal papillary necrosis due to Occlusion of
vasa recta and medullary vessels

9.  Hematuria due to Medullary vascular occlusion by
sickled RBCs; rarely renal medullary carcinoma,
usually painless and self-limited, 80 – 90%
unilateral
 AKI due to volume depletion; severe sepsis and
rhabdomyolysis
 CKD due to progressive parenchymal damage and
chronic glomerular disease

10. Investigations
 Mainly based on clinical manifestations and
exclusion.
 Routine, outpatient investigations: U&Es, SCr,
urinalysis and uACR/uPCR, FBC, reticulocytes ,
LFTs.
 Heavy proteinuria : immunological and
serological screen to rule out other causes
(Parvovirus serology) may cause nephrotic
syndrome

11.  Imaging studies:
 kidney ultrasound to rule out obstructive
uropathy
 Intravenous urography and CT scan with contrast
 Increased echodensity.
 Calyceal clubbing with papillary necrosis
 MRI scans : Renal iron deposition noted on

12.  Renal biopsy may be necessary (particularly if
rapid onset)
 There is no pathognomonic lesion for SCN .
 Glomerular hypertrophy with distended
capillaries and FSGS which is most common lesion
not specific to SCN.

13.  Papillary necrosis in
sickle cell disease:
Intravenous urography
shows abnormal calyces
with filling defects
(arrows).
 Focal segmental
glomerulosclerosis in
sickle cell nephropathy.
There is segmental
sclerosis in the upper
half of the glomerulus.

14. Diagnostic and Therapeutic approach
 Proteinuria (>1 g/day)
1. Non-nephrotic: Consider biopsy: rule out 
immune glomerulopathy
2. Nephrotic: Consider biopsy: rule out  renal
vein thrombosis, MCNS and immune
glomerulopathy
 Angiotensin converting enzyme inhibitors or
angiotensin receptor blockers is the
treatment of choice.

15.  Gross hematuria
 Rule out  other coagulopathies and other
nephropathies
 Local causes of bleeding
 Papillary necrosis and Medullary carcinoma
 Mild: Good hydration, alkalinization of urine
 Severe: Epsilon-aminocaproic acid (EACA) , local
embolization, nephrectomy (rarely)

16.  Acute renal failure
 Rule out hypovolemia, sepsis, nephrotoxic
drugs, rhabdomyolysis, obstruction by blood clots,
GN and hepatorenal
 Correct of pre-renal factors
 Stop any nephrotoxic drugs
 Treat source of sepsis
 Rule out obstruction
 Urine alkalinization in case of rhabdomyolysis
 RRT if needed

17.  End-stage renal disease: like any patient must
correct
 Renal osteodystrophy , electrolyte disturbances
and hypocalcemia and hyperphosphatemia
 Low-protein diet
 Calcium supplementsa and Phosphate binders
 Dialysis and Renal transplantation

18. Notes
 Patient may suffer from bacteriuria:
 Autosplenectomy (encapsulated organisms)
 Abnormal dilute
 Alkaline urine (more favorable for bacterial growth
compared with hypertonic and acidic urine)
 Papillary necrosis.
 Renal infarction

19.  Most patient with low blood presuure
 Reduce vascular reactivity
 Compensatory VD associated with microvascular
disturbances from the sickling cells and thrombotic
complications.
 Elevated levels of prostaglandins and nitric oxide
 The renal sodium and water wasting associated with
suboptimal medullary concentrating activity.
 Blood pressure in “normal” range for the general
population may represent hypertension in patients
with SCD.

20.  SCD and sickle cell trait (SCT)
 Kidney manifestations are common and severe in SCD
but Renal medullary carcinoma more in patients with
SCT
 Renal medullary carcinoma typically presents in young
patients (20 to 30 years old) with aggressive metastatic
at the time of diagnosis.
 Median survival is 3 months following diagnosis, Present
with hematuria, flank pain, and/or abdominal mass.

21.  Special considerations for patients with
anemia in CKD and SCD
 Same line of treatment like CKD without SCD.
 Patient has lower Hb levels and higher ESA
requirements than their anemic CKD patients.
 Transfusions are more so take care of iron
overload and sensitization for future kidney

22. Causative factors of FSGS in SCD
 Hyperfiltration of cortical nephrons  (VD
prostaglandins, increased NO , cytokines from
damaged vascular endothelium)
 Increased production of oxidative factors
 Chronic exposure of tubular epithelium to high
levels of filtered plasma proteins
 Autologous immune-complex nephritis

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