Overview.
Kidney damage due to sickle cell disease is called sickle cell nephropathy. Sickle cell disease is a hemoglobinopathy caused by abnormal hemoglobin, with hemolytic anemia being the most common, accompanied by hypogranulocytosis. It is more common in females than in males, especially in adolescents, and is more common between the ages of 6 and 15. It suggests that the patient has abnormal renal tubular function.
Etiology
Sickle cell disease is due to genetic inheritance of an abnormality in the β-pearl protein chain subunit of hemoglobin. Patients who receive two identical genes for abnormal hemoglobin from both parents, i.e., purebloods, have red blood cells that lack normal hemoglobin (HbA) and are replaced by abnormal hemoglobin (HbS), called sickle cell anemia or sickle cell disease. Patients who receive an abnormal hemoglobin gene from one parent, i.e., heterozygotes, and whose red blood cells contain both normal and abnormal hemoglobin but are more than 50% normal, are called sickle cell predisposition.
Symptoms
1. Sickle cell disease
(1) Pure heterozygous sickle cell disease There are varying degrees of hemolytic anemia and mild jaundice. Vascular occlusion crisis is its prominent manifestation, often severe pain in the trunk and limbs, including visceral, bone, joint and muscle pain, especially in the metacarpal, tarsal and phalangeal infarcts are common, infection, dehydration, hypoxia and acidosis are the triggers. Infections, dehydration, hypoxia and acidosis are the triggers. Visceral and cerebrovascular infarcts present with corresponding signs and symptoms.
(2) Heterozygous sickle cell disease is usually asymptomatic, without hemolytic anemia, so it is also called sickle cell tendency. Microcirculatory disorders occur only under severe hypoxia, mainly in the straight blood vessels of the renal medulla, because of the presence of significant hypertonicity there, which makes the red blood cells easy to dehydrate, coupled with the physiological characteristics of low oxygen tension and low pH, resulting in sickling of red blood cells, stagnation of renal medullary blood flow, and even vascular occlusion. In severe cases, renal papillary necrosis can occur.
2. Hematuria
Hematuria can occur in pure or heterozygous subtypes. Hematuria is the most common manifestation of renal damage, which can be visual hematuria, but mainly microscopic hematuria. It may be caused by microscopic necrosis of renal medulla and renal papilla, or glomerulonephritis.
3. Nephrotic syndrome
Typical nephrotic syndrome may occur in sickle cell disease.
4. Renal tubular insufficiency
In patients with sickle cell anemia, renal tubular lesions are more common, and renal hypoconcentration can be seen in the early stage, followed by a decrease in the concentration and dilution capacity, and the emergence of isotonic urine. The disease is reversible in the early stages, and in the later stages, irreversible damage to the renal medulla occurs due to chronic ischemia, with permanent polyuria, nocturia, and other urinary concentrative dysfunctions. Distal tubular acidosis can occur, mostly incomplete.
5. Hyperuricemia
In this disease, the metabolism of erythrocytes is 6-8 times higher than that of normal people, and uric acid is generated excessively, but its clearance rate is increased, so gouty arthritis will not occur.
6. Renal failure
Acute renal failure may occur due to renal vascular occlusion and acute intravascular hemolysis. 18% of the patients may develop to the end stage of chronic renal failure due to glomerulopathy and multiple episodes of sickle crisis.
Examination
1. Laboratory examination
(1) Blood tests There are varying degrees of hemolytic anemia and mild jaundice in which red blood cells lack normal hemoglobin (HbA) and are replaced by abnormal hemoglobin (HbS). Hemoglobin electrophoresis shows a large amount of HbS and a positive sickle cell formation test.
(2) Urine examination shows hematuria, proteinuria, and hypotonic polyuria; hematuria can occur in this disease regardless of the pure or heterozygous type, and may appear as hematuria in the naked eye, but microscopic hematuria is predominant. Typical nephrotic syndrome can occur in sickle cell disease, and the laboratory changes of nephrotic syndrome can appear at this time.
2. Other auxiliary tests
(1) Renal biopsy suggests that the glomeruli of patients with sickle cell anemia are enlarged and sloughed, sickle cells fill the tubular lumen, and the mesangial cells have different degrees of hyperplasia. Due to the thickening of the basement membrane of the glomerular capillaries, mild to moderate hypertrophy of the vessel wall can be seen, and in the patients with the combined nephrotic syndrome, an increase in the glomerular lobes is seen, which suggests that glomerulo-capillary vasculitis exists. Iron deposition was seen in epithelial and endothelial cells. Segmental glomerulosclerosis and membranous nephropathy may also be seen.
(2) Electron microscopy suggests that 25 nm particles are concentrated in the intercapillary and subepithelial areas, and mesangial cell hyperplasia and interstitial changes in the peripheral mesangium are common.
(3) Immunologic examination Immunofluorescence is mostly negative, and in some patients, IgG and C3 are irregularly deposited around the capillaries. These cases are mostly nephrotic syndrome, membranous or tethered capillary glomerulonephritis.
Diagnosis
The main diagnostic basis:
1. anemia
Hemoglobin is usually in the range of 70-80 g/l for hemolytic anemia. The disease should be suspected if accompanied by paroxysmal severe pain in the trunk or limbs. Reticulocytes are often up to 10%.
2. Positive erythrocyte sickling test
Mix the patient’s blood with sodiummetabisulfite solution, deoxygenate the blood to induce erythrocyte sickling, and sickle red blood cells can be seen on microscopic examination. Or for hemoglobin solubilization test, add phosphate solution into the above mixture, normal hemoglobin solubilization without precipitation; abnormal hemoglobin solubility is low and turbid precipitation occurs.
3. Hemoglobin electrophoresis
Hemoglobin electrophoresis shows abnormal hemoglobin (HbS). In hemoglobin electrophoresis showing a large amount of HbS, a positive sickle cell formation test confirms the diagnosis of sickle cell tendency, sickle cell disease combined with hematuria, proteinuria, hypotonic polyuria, nephrotic syndrome, pyelonephritis, tubular dysfunction, and acute and chronic renal failure and other manifestations of renal damage can diagnose this disease.
Differential diagnosis
It should be distinguished from other types of anemia and renal lesions.
Treatment
The treatment of this disease includes the treatment of sickle cell disease and the treatment of kidney damage. The treatment of sickle cell disease focuses on anti-sickling, relieving sickling, lowering blood viscosity and symptomatic treatment, while avoiding factors that aggravate sickling; renal damage focuses on symptomatic treatment.
Although there is no special treatment for this disease, if patients can be instructed to avoid sickling triggers, strengthen self-care, pay attention to warmth, avoid exertion, etc., it will be beneficial to prevent the occurrence of acute crisis and improve the prognosis. The combination of Chinese and Western medicine can be utilized, with Western medicine applying vasodilators, painkillers, blood transfusions, antibiotics and oxygen administration, etc., while Chinese medicine practitioners can choose to use Astragalus, Salviae Miltiorrhizae and Rhizoma Ligustici Chuanxiong for long-term use or according to the above mentioned diagnosis and use of medication, which would have a better efficacy.
1. Drug therapy
Drugs may reverse sickling, but cannot correct the genetic defect. Drugs against sickling can release sickling and reduce blood viscosity, thus improving microcirculation, increasing blood perfusion, improving tissue oxygen supply, reducing kidney damage and alleviating clinical symptoms. Heterozygous sickle cell disease generally does not require treatment, because the heterozygote solubility is 35% to 68%, and the degree of hemolysis is low. The following anti-sickle change drugs can be used for reference:
(1) Zinc sulfate Anti-sickling effect, but prolonged use will occur hypocoppermia.
(2) Dihydroergotoxine (Hitechin, hydroergotoxine) is a vasodilator, which helps to relieve the spasm of small arteries caused by sickle-change erythrocyte coagulation, unclog the microcirculation, improve the hypoxic state, and reduce the pain symptoms.
(3) 30% urea sucrose solution interferes with the process of sickle cell formation, and is contraindicated in patients with renal insufficiency.
(4) Methyl diacetylenediimine By acting on hemoglobin and erythrocyte membrane, it makes erythrocytes less prone to potassium loss and improves oxygen affinity.
(5) Carbamoyl Phosphate Improves the oxygen affinity of hemoglobin and has an anti-sickle effect. The substance can be synthesized and utilized in the body and degraded in normal metabolism, and is a promising drug for the treatment of this disease.
(6) 5-Azacytidine It has an anti-sickle change effect, but has a certain degree of toxicity.
(7) Nootropyl (containing piracetam and fennelacetam) has the effect of consolidating the therapeutic effect on general patients.
2. Avoid factors that aggravate sickling
Factors such as hypoxia, exertion, infection, dehydration, fever, cold or acidosis can promote erythrocyte sickling. Avoid activities in hypoxic environment (high mountains, deep wells). In some patients, sickling is exacerbated at night, infection and cold, and a large number of hemolysis, even induced acute crisis. When cold, vasoconstriction, blood flow is slow, blood oxygenation capacity is reduced, and sickling of red blood cells occurs, so it is necessary to prevent cold. Early control of infection, lung infection or heart failure, adequate oxygenation, maintaining high oxygen saturation is also important. Dehydration, which concentrates the blood to a hypertonic state, also aggravates sickling, so fluids should be replenished promptly. Acidosis is also present and should be corrected with oral or intravenous sodium bicarbonate. In addition, the following factors will aggravate the disease, such as pregnancy, abdominal surgery, excessive surgical bleeding and anesthesia is too deep (partial pressure of blood oxygen is lowered), etc., general anesthesia surgery to keep the airway open, adequate oxygen supply, to ensure that the oxygen oxygenation of the blood, such as local anesthesia is more appropriate. In short, from all aspects of attention to strengthen the prevention and treatment.
3. Treatment of acute crisis
Due to the role of certain triggering factors suddenly severe hemolysis produce acute crisis, as soon as possible transfusion of blood and fluids, keep warm. If the crisis persists, it is feasible to use blood exchange therapy to reduce HbS to 25%~50%. Oxygen or hyperbaric oxygen has a certain effect, the deformed red blood cells are reversible, and when recombined with oxygen, its normal form is restored.
4.Symptomatic treatment
(1) Drink more water, high sodium diet Make water intake increase, or intravenous fluid supplementation, intravenous low molecular dextran plus scopolamine. It is more favorable to reduce blood viscosity and improve microcirculation of renal medulla. There are reports that long-term oral administration of Salvia miltiorrhiza and henbane can reduce osteoarthralgia and abdominal pain, and can stabilize the condition without side effects.
(2) Scopolamine (654-2) Intravenous injection of scopolamine for those with critical symptoms. Scopolamine (654-2) can increase the fluidity of erythrocyte membrane, improve the rigidity of erythrocytes, protect the cell membrane, prolong the life span of erythrocytes, and improve the phenomenon of hemolysis and infarction.
(3) Application of diuretics and hemostatic drugs If hematuria is obvious and lasts for a long time, medullary loop diuretics such as furosemide and bumetanide (butyramide) or osmotic diuretics such as mannitol can be used, and sodium bicarbonate can be taken orally to alkalinize the urine. Aminocaproic acid or Yunnan Baiyao can also be used to stop bleeding.
(4) Application of antibiotics When there are urinary tract infections and pyelonephritis, antibiotics such as ampicillin (benzylpenicillin), cephradine, cefoperazone and so on should be used in time to control the infection. The application of antibiotics is very important to protect the kidney and improve the prognosis. Prevention of infection, low-salt diet and drinking plenty of water are also important treatment measures. Children with fever should be rehydrated in time to prevent the occurrence of crisis.
(5) The application of analgesics When the pain is severe, oral aspirin, acetaminophen (paracetamol), codeine and so on can be taken. Vitamin E and vitamin C are antioxidants, which can reduce the response of sickle cells to peroxidation.
(6) the application of angiotensin converting enzyme inhibitors (ACEI) can reduce the glomerular capillary pressure, improve the permeability of the basement membrane, can reduce the excretion of urinary protein, because the damage factors of renal disease may be mainly hemodynamic factors, long-term ACEI class of drugs can slow down the development of the lesion, to prevent and delay the onset of renal failure.
(7) Treatment of anemia Chronic hemolytic anemia may be transfused as appropriate, mild and moderate anemia may not be transfused, usually the patient has adapted to chronic anemia, long-term blood transfusion will bring more disadvantages. Erythropoietin is often ineffective. Folic acid should be added in pregnancy. Early moderate blood transfusion in pediatric patients can correct anemia and also help to correct urine concentration dysfunction.
(8) Treatment of renal tubular acidosis Oral sodium bicarbonate or citrate combination to correct.
(9) Dialysis and renal transplantation In patients with sickle cell anemia, the survival rate of renal transplantation is basically similar to that of common renal transplantation. If renal failure occurs in such patients, dialysis and renal transplantation can be practiced, but the long-term survival rate is lower due to multi-system complications. In terms of post-transplant mortality, renal transplantation is recommended, but sickle cell crisis still occurs in more patients after transplantation.
(10) Genetic engineering Genetic engineering can be applied to sickle cell disease when available.