Published in IJCP December 2024
Review Article
Challenges and Solutions for Dialysis in Sickle Cell Nephropathy
December 10, 2024 | Sotubo Sotomiwa, Sourabh Sharma, Amisu Mumuni, Odeyemi Ayoola, Banjoko Oluwole, Adekoya Adebowale, Awobusuyi Olugbenga
Nephrology
     


Abstract

Sickle cell disease (SCD) is a hereditary condition characterized by abnormal hemoglobin S (HbS) and intermittent vaso-occlusive crises. Patients with SCD often develop sickle cell nephropathy (SCN), a significant cause of end-stage kidney disease (ESKD) that requires dialysis as a preferred mode of renal replacement therapy. These patients experience higher mortality rates than those with ESKD from other causes due to the unique challenges dialysis physicians face in managing SCN cases. This review discusses these challenges and proposes potential solutions.

Keywords: Sickle cell disease, sickle cell nephropathy, sickle cell crisis, end-stage kidney disease, dialysis, hemodialysis, peritoneal dialysis

Sickle cell nephropathy (SCN) is a crucial contributor to chronic kidney disease (CKD), which, despite its silent progression, significantly impacts survival. Toward the later stages of life, most individuals with sickle cell disease (SCD) require kidney replacement therapy. Although native kidney function is often preserved, kidney disease may go unrecognized, or the need for replacement therapy might be delayed.

SCD is a genetic disorder characterized by the presence of abnormal hemoglobin S (HbS) and recurrent vaso-occlusive crises (VOC). In SCD, the renal medulla is particularly vulnerable to damage when renal blood flow decreases, especially during dehydration, hypovolemia, and chronic anemia. Such events result in specific renal structural changes associated with SCD. CKD occurs in 5% to 18% of the general SCD population, increasing to nearly 30% in patients over 40 years of age1. SCN contributes substantially to premature mortality, accounting for 16% to 18% of deaths2,3.

Studies indicate a higher 1-year mortality rate following dialysis initiation in SCD patients, though early nephrology care can help reduce this mortality2. Rates of CKD and progression to end-stage kidney disease (ESKD) have risen significantly over the past decade, particularly among African American patients. Although CKD is prevalent in SCD and associated with high mortality3, dialysis treatment for CKD in these patients remains under-examined. Here, we present the dialysis management challenges specific to this patient population.

CHALLENGES IN DIALYSIS FOR SICKLE CELL NEPHROPATHY

The authors, with experience in managing SCN, face various dialysis-related challenges in ESKD cases. These challenges are outlined in Table 1, emphasizing the need to raise awareness among nephrologists and dialysis physicians regarding the elevated mortality risk in SCN-ESKD patients compared to non-SCD patients on dialysis4.

Table 1. Challenges of SCN-ESKD on Dialysis and Possible Solutions

Challenges in SCN-ESKD

Underlying mechanism

Possible solutions

Hemodynamic instability

Relative hypotension due to salt-losing tubulopathies, anemia

·   Low blood flow rate with longer duration of dialysis to improve dialysis adequacy

·   Optimize hemoglobin

·   SLED

·   Peritoneal dialysis can be adopted for patients with significant residual kidney function

Poor vascular access

Atherosclerosis due to endothelial dysfunction, chronic inflammation, and platelet activation

·   Hydroxyurea to increase HbF and nitric oxide

·   Antiplatelet can be considered if there is significant cardiovascular risk

·   Consider peritoneal dialysis is vascular access is a challenge

Anemia

·   Reduced EPO

·   Reduce red cell lifespan

·   Uremic toxins

·   High-dose EPO

·   Exchange blood transfusion

Increase risk of sickle cell crisis

Refer to Table 2

·   Refer to Table 2

Poor transplantation outcome

·   High sensitization

·   Comorbidities (e.g., pulmonary hypertension, cardiomyopathy)

·   Increased thrombotic risk

·   Careful patient selection and addressing comorbidities

·   Transfuse only when necessary, using leukocyte filter

SLED = Sustained low efficiency dialysis; HbF = Fetal hemoglobin; EPO = Erythropoietin.

·   Hemodynamic instability: Individuals with SCN-ESKD on dialysis have a heightened risk of hypotension due to relatively low blood pressure and anemia, possibly linked to salt-losing tubulopathy5. This condition limits blood flow during dialysis, often resulting in inadequate treatment. Extending dialysis duration can improve adequacy6,7. Hemoglobin levels must be optimized but should not exceed 10 g/dL to minimize the risk of sickle cell crises8. Conditions like sickle cell cardiomyopathy and anemia-related heart failure also contribute to hemodynamic instability9. Sustained low efficiency dialysis (SLED) and peritoneal dialysis may serve as an optimal alternative for such cases8.

·   Vascular access: SCN-ESKD patients often exhibit poor compliance with arteriovenous fistula (AVF) creation and have high rates of primary AVF failure. Studies show better survival outcomes in patients using AVF or grafts for dialysis10. However, AVF can exacerbate hemodynamic instability, particularly in patients with pulmonary hypertension11. AVF use also increases the risks of stenosis, thrombosis, and infection11. In cases of access failure, peritoneal dialysis is a viable alternative with less hemodynamic instability8.

·   Anemia: Managing anemia in SCN-ESKD presents significant challenges due to resistance to erythropoietin (EPO) therapy, with unachievable targets even at high doses. High EPO doses are linked to elevated mortality and hospitalization risks in SCD4 and may increase the frequency of VOC8,12. Most patients require repeated blood transfusions to reach target hemoglobin levels, posing additional risks of infection and iron overload13.

·   Sickle cell crisis: SCN is associated with an elevated risk of VOC8. Table 2 outlines the various factors contributing to this increased risk, alongside suggested solutions14-21.

Table 2. Factors that can Precipitate Sickle Cell Crisis in SCN-ESKD on Dialysis and Possible Solutions14-21

Factors precipitating sickle cell crisis

Challenges in sickle cell nephropathy

Possible solutions

Cold weather

Dialysate temperature

·   Keep dialysate temperature above 36.5°C

·   Do not use cool dialysate in intradialytic hypotension

Physical and psychological stress

Exertion, Depression

·   Keep stress-free environment

·   Start antidepressants if needed

Infections

·   Atypical bacteria (Chlamydia/Mycoplasma)

·   Viruses (RSV/Parvovirus B19)

Encapsulated bacteria

High risk of infections in CKD (dialysis catheters, blood-borne infections, decreased immunity, etc.)

·   Strict aseptic precautions

·   Timely vaccination against Pneumococcus and influenza

Dehydration

Higher risk of dehydration (restricted fluid intake/heat stress/high target ultrafiltration)

·   Bioimpedance analysis for dry weight

·   Avoid heat stress

·   Weight charting

Low oxygen tension

Respiratory failure (diffusion failure in pulmonary edema and pneumonia or hypoventilation in uremic encephalopathy)

·   Strict thrice weekly hemodialysis

·   Maintain dry weight

·   Avoid chest infections by applying precautions like face mask, etc.

Acidosis

Metabolic acidosis

·   Regular monitoring of bicarbonate levels

·   Early dialysis initiation

·   Maintain [HCO–3] >23 mEq/L

Pregnancy

Most patients counseled to avoid pregnancy

·   Regular counseling

·   Contraceptive use

Alcohol and Smoking

Most patients counseled to avoid substance abuse

·   Regular counseling

·   Quit smoking and alcohol

Shock

Hypovolemic and cardiogenic shock

·   Regular follow-up

·   Regular cardiology referral

·   Avoid intradialytic hypotension

Folic acid deficiency

Common in strict vegetarians

Dietary restrictions

·   Avoid strict dietary restrictions

·   Regular monitoring of serum folate levels

RSV = Respiratory seasonal virus; CKD = Chronic kidney disease; HCO–3 = Bicarbonate.

·   Transplantation: Transplant rates among SCN-ESKD patients are lower, despite the significant survival benefits4,22. One-year post-transplant survival is lower in SCN-ESKD compared to non-SCN populations but remains significantly better than in those on dialysis23. Increased post-transplant risks, including thrombosis and infection, affect both graft and patient survival24. Perioperative blood transfusions to maintain hemoglobin above 10 g/dL and HbS below 30% are recommended to improve post-transplant outcomes24.

CONCLUSION

In conclusion, dialysis physicians must be aware of the specific challenges in managing SCD-ESKD patients and recognize the factors that can precipitate sickle cell crises in these cases. An in-depth understanding of these conditions and appropriate management strategies are essential for early diagnosis, prompt treatment, and improved mortality and health outcomes in this ESKD population.

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