Renal Failure: A complication of Sickle Cell Disease

WhatsApp Discussion on held on 28th August 2020

Facilitator: Dr. Joseph Agbi

Key words 

People living with sickle cell disease: PLWSCD

Sickle cell diseases: SCD

Introduction

The collective term for kidney challenges encountered in Sickle Cell Disease (SCD) is called “Sickle Cell Nephropathy (SCN)”. This means abnormal renal function as a result of sickle cell disease.

The most common effect red cell sickling has to organs is hypoxia (low oxygen) and anaemia (from low HB levels). Anaemia causes infarction or organ damage. Hypoxia may cause an acidic internal environment which further heightens damage.

Anatomical Areas of the Kidneys

Anaemia causes infarction or organ damage and Hypoxia may cause an acidic internal environment which further heightens damage in the kidney.

The kidney itself has different anatomical areas that can be affected and the key areas to focus on are:

1. The glomerulus.

2. Collecting tubes.

Glomerulus: this is like a sieve that filters what the kidney is able to excrete. Because of the anemia, the body tries to compensate by increasing blood flow and further increases what is filtered. This increases urine clearance and thus people with SCD urinate more often.

Asides this, other changes take place in the glomerulus that make it possible to excrete molecule that should otherwise not be excreted in urine such as protein and blood.

Collecting Tubules (tubes): these are very tiny tunes in the kidney that help to filter and re-filter until urine has its normal concentration. Sickling of cells in vessels supplying the kidney causes changes in this tubule and make their function impaired thus people with SCD have an impaired ability to concentrate urine. This furthers the risk of frequent Urinary Tract Infection (UTI) encountered a lot.

So, when do these changes actually begin?

Well from as soon as symptoms of SCD are noticeable in childhood it is safe to assume that kidneys begin to get affected. This goes on until adulthood.

Onset of chronic kidney disease usually occurs between ages 30 to 40 following long standing changes tolerated by the kidneys. Statistically, 5 to 18 % of people with SCD develop CKD at this ages and about 11 % developing ESRD (End Stage Renal Disease).

Chronic Kidney Disease (CKD).

Chronic kidney disease describes gradual decline in kidney function and this is assessed using a renal function test which checks creatinine levels, GFR (Glomerulus Filtration Rate) or renal clearance among others.

CKD occurs in stages with the kidneys having normal function of Cr values are within normal range and GFR is >90

Risk Factor for Profession of CKD

It has been proven that protein leakage (called proteinuria) is the number one risk factor for progression of CKD. This is because protein leak damages the glomerulus further. So, the greater the amount of proteins in urine the faster CKD will progress.

By early adulthood, most patients with SCD will detect proteins in urine. But that does not mean CKD is progressing. It depends on how much protein leakage occurs, and blood in urine has a worse implication because it has heavier proteins.

Proteins are of different sizes while blood occupies the larger spectrum. Blood in urine when doing a dipstick, in the absence of obvious bleeding often means kidneys are well damaged.

End Stage Renal Disease (ESRD)

A smaller fraction of people with CKD progress to ESRD. At this stage renal function is down to 10% and dialysis may be required. The number one risk factor for progression to ESRD in people with CKD is also proteinuria. Heavy amount of proteinuria makes progression faster.

Also, anemia from CKD is another risk factor because the kidney helps to make blood, once CKD progresses to a particular level, anemia worsens regardless of blood transfusion. This worsening anemia in turn damages the kidney. Hemolysis release more damaged red cells which are excreted in the kidney accelerating progression to ESRD.

Prevention and MANAGEMENT

The goal in Sickle Cell Nephropathy is to avoid progression to End Stage Renal Disease.

Many of the changes that occur can’t be avoided because it’s part of the spectrum of Sickle Cell Disease but Chronic Kidney Disease and End Stage Renal Failure can be avoided.

  1. Be aware: These changes happen irrespective of whether one is aware or not. So better be aware.
  2. Early monitoring. I have before mentioned that full blood counts and PCV (Packes Cell Volume) is not all there is. Urine tests are very important. Once in Early adulthood, have regular urine test to monitor renal function and proteins. Also, have routine hematology clinic visits. Hematologist know how to monitor growth and when to request for important tests.
  3. Hydroxyurea: This drug has been proven to slow down changes in kidneys to nearest minimum, especially when it successfully raises the level of hemoglobin. Fetal hemoglobin has been proven to be very protective of changes to kidneys. So early commencement of hydroxyurea and in particular routine monitoring for increase in fetal hemoglobin is recommended.
  4. Avoiding crisis: Although changes to kidneys will occur even without full blown crisis because there’s constant microvascular sickling, avoiding crises as much as possible is better.  Full blown crises or illnesses can worsen renal function dramatically especially if blood levels drop acutely from anemia. Hypotension can cause acute kidney injury. Although this can be reversed, latent damages are often incurred.

Managing Increasing Proteinuria

Once protein leak is detected to be above a particular level, the following medications and measures must be commenced

  1. Hydroxyurea.
  2. ACEIs or Angiotensin Converting Enzyme Inhibitors. ACEIs have been used to reduce proteinuria with success especially in people with high diabetes, another disease that causes protein leak. So ACEIs can be taken too when prescribed
  3. Diet regulation: Especially low salt diet, also, protein intake needs to be regulated.  Now we know proteins are the building blocks in the body and people with SCD normally have small mass, so there’s a bit of grey area if proteins should be regulated in people who just have proteinuria and no CKD. However once CKD is reached, protein intake must be regulated to a max of 1.5g/kg per day. So, someone who weighs 50kg will need to regulate protein intake to 75g per day of this person has CKD.
  4. Hydration: Without CKD water should be taken liberally to clear urine Chanel’s and improve blood flow. Once there is onset of CKD especially if CKD has progressed much, fluid intake will be restricted to avoid overloading the heart.
  5. Blood transfusion remains central to management of sickle cell disease. As much as anemia can cause decline in kidney function, blood transfusion can rejuvenate kidney function. So, all efforts must be made to keep Haemoglobin (HB) as optimal as possible.

Managing End Stage Renal Disease (ESRD)

With gradual decline and ESRD sets in, options like dialysis and kidney transplant can be considered.

Sickle cell disease is not a contraindication for kidney transplant as formerly thought because it was felt it would not make much difference. However, this depends on a lot of factors and it is advised to undertake transplant once the means is available

In Summary;

Sickle Cell Nephropathy (SCN) involves changes to renal function due to Sickle Cell Disease (SCD).

Changes start from early ages.

Chronic Kidney Disease (CKD) results from uncontrolled proteinuria.

End Stage Renal Disease (ESRD) occurs from progressive Chronic Kidney Disease (CKD).

Hydroxyurea is gold standard for management of Sickle Cell Nephropathy (SCN).

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