Sickle cell nephropathy
Encyclopedia
Sickle cell nephropathy is a type of nephropathy
associated with sickle cell disease, it causes renal complications as a result of sickling of red blood cells in the microvasculature. The hypertonic and relatively hypoxic
environment of the renal medulla
, coupled with the slow blood
flow in the vasa recta
, favors sickling of red blood cells, with resultant local infarction
(papillary necrosis). Functional tubule defects in patients with sickle cell disease are likely the result of partial ischemic injury to the renal tubules.
Also the sickle cell disease in young patients is characterized by renal hyperperfusion, glomerular hypertrophy
, and hyperfiltration. Many of these individuals eventually develop a glomerulopathy
leading to glomerular proteinuria
(present in as many as 30%) and, in some, the nephrotic syndrome
. Co-inheritance of microdeletions in the -globin
gene
( thalassemia
) appear to protect against the development of nephropathy
and are associated with lower mean arterial pressure
and less proteinuria
.
Mild azotemia
and hyperuricemia
can also develop. Advanced renal failure and uremia occur in 10% of cases. Pathologic examination reveals the typical lesion of "hyperfiltration nephropathy" namely, focal segmental glomerular sclerosis. This finding has led to the suggestion that anemia
-induced hyperfiltration in childhood
is the principal cause of the adult
glomerulopathy. Nephron
loss secondary to ischemic injury also contributes to the development of azotemia
in these patients.
In addition to the glomerulopathy described above, renal complications of sickle cell disease include cortical infarcts leading to loss of function, persistent hematuria
, and perinephric hematomas. Papillary
infarcts, demonstrable radiographically in 50% of patients with sickle trait, lead to an increased risk of bacterial infection
in the scarred
renal tissues and functional tubule abnormalities. Painless gross hematuria occurs with a higher frequency in sickle trait
than in sickle cell disease and likely results from infarctive episodes in the renal medulla. Functional tubule abnormalities such as nephrogenic diabetes insipidus
result from marked reduction in vasa recta blood flow, combined with ischemic tubule injury. This concentrating defect places these patients at increased risk of dehydration
and, hence, sickling crises. The concentrating defect also occurs in individuals with sickle trait. Other tubule defects involve potassium
and hydrogen
ion excretion
, occasionally leading to hyperkalemic metabolic acidosis
and a defect in uric acid
excretion which, combined with increased purine
synthesis in the bone marrow
, results in hyperuricemia
.
and patient survival in renal transplant recipients with sickle nephropathy is diminished as compared to those with other causes of end-stage renal disease.
Nephropathy
Nephropathy refers to damage to or disease of the kidney. An older term for this is nephrosis.-Causes:Causes of nephropathy include administration of analgesics, xanthine oxidase deficiency, and long-term exposure to lead or its salts...
associated with sickle cell disease, it causes renal complications as a result of sickling of red blood cells in the microvasculature. The hypertonic and relatively hypoxic
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
environment of the renal medulla
Renal medulla
The renal medulla is the innermost part of the kidney. The renal medulla is split up into a number of sections, known as the renal pyramids. Blood enters into the kidney via the renal artery, which then splits up to form the arcuate arterioles. The arcuate arterioles each in turn branch into...
, coupled with the slow blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
flow in the vasa recta
Vasa recta
In the blood supply of the kidney, the vasa recta renis form a series of straight capillaries in the medulla...
, favors sickling of red blood cells, with resultant local infarction
Infarction
In medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
(papillary necrosis). Functional tubule defects in patients with sickle cell disease are likely the result of partial ischemic injury to the renal tubules.
Also the sickle cell disease in young patients is characterized by renal hyperperfusion, glomerular hypertrophy
Hypertrophy
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It should be distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number...
, and hyperfiltration. Many of these individuals eventually develop a glomerulopathy
Glomerulopathy
Glomerulopathy is a term used to describe a disease affecting the glomeruli of the nephron.It can refer to a process that is inflammatory or noninflammatory. Because the term "glomerulitis" exists for inflammatory conditions, "glomerulopathy" sometimes carries a noninflammatory implication....
leading to glomerular proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
(present in as many as 30%) and, in some, the nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
. Co-inheritance of microdeletions in the -globin
Globin
Globins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
( thalassemia
Thalassemia
Thalassemia is an inherited autosomal recessive blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin...
) appear to protect against the development of nephropathy
Nephropathy
Nephropathy refers to damage to or disease of the kidney. An older term for this is nephrosis.-Causes:Causes of nephropathy include administration of analgesics, xanthine oxidase deficiency, and long-term exposure to lead or its salts...
and are associated with lower mean arterial pressure
Mean arterial pressure
The mean arterial pressure is a term used in medicine to describe an average blood pressure in an individual. It is defined as the average arterial pressure during a single cardiac cycle.-Calculation:...
and less proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
.
Mild azotemia
Azotemia
Azotemia is a medical condition characterized by abnormally high levels of nitrogen-containing compounds, such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood...
and hyperuricemia
Hyperuricemia
Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...
can also develop. Advanced renal failure and uremia occur in 10% of cases. Pathologic examination reveals the typical lesion of "hyperfiltration nephropathy" namely, focal segmental glomerular sclerosis. This finding has led to the suggestion that anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
-induced hyperfiltration in childhood
Childhood
Childhood is the age span ranging from birth to adolescence. In developmental psychology, childhood is divided up into the developmental stages of toddlerhood , early childhood , middle childhood , and adolescence .- Age ranges of childhood :The term childhood is non-specific and can imply a...
is the principal cause of the adult
Adult
An adult is a human being or living organism that is of relatively mature age, typically associated with sexual maturity and the attainment of reproductive age....
glomerulopathy. Nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
loss secondary to ischemic injury also contributes to the development of azotemia
Azotemia
Azotemia is a medical condition characterized by abnormally high levels of nitrogen-containing compounds, such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood...
in these patients.
In addition to the glomerulopathy described above, renal complications of sickle cell disease include cortical infarcts leading to loss of function, persistent hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
, and perinephric hematomas. Papillary
Renal papilla
In the kidney, the renal papilla is the location where the medullary pyramids empty urine into the minor calyx. Histologically it is marked by medullary collecting ducts converging to form a duct of Bellini to channel the fluid. Transitional epithelium begins to be seen.-Role in disease:Some...
infarcts, demonstrable radiographically in 50% of patients with sickle trait, lead to an increased risk of bacterial infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
in the scarred
Scarred
Scarred is a television program that debuted on MTV on April 10, 2007. On each episode of Scarred, several real-life risk-takers share the stories of how they were scarred or injured while attempting dangerous stunts on primarily skateboards, but occasionally on in-line skates, skis, snowboards,...
renal tissues and functional tubule abnormalities. Painless gross hematuria occurs with a higher frequency in sickle trait
Trait
Trait may refer to:* Trait, a characteristic or property of some object* Trait , which involve genes and characteristics of organisms* Trait theory, an approach to the psychological study of personality...
than in sickle cell disease and likely results from infarctive episodes in the renal medulla. Functional tubule abnormalities such as nephrogenic diabetes insipidus
Diabetes insipidus
Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
result from marked reduction in vasa recta blood flow, combined with ischemic tubule injury. This concentrating defect places these patients at increased risk of dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
and, hence, sickling crises. The concentrating defect also occurs in individuals with sickle trait. Other tubule defects involve potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
and hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
ion excretion
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
, occasionally leading to hyperkalemic metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
and a defect in uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
excretion which, combined with increased purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
synthesis in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, results in hyperuricemia
Hyperuricemia
Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...
.
Treatment
Management of sickle nephropathy is not separate from that of overall patient management. In addition, however, the use of ACE inhibitors has been associated with improvement of the hyperfiltration glomerulopathy. Three-year graftMedical grafting
Grafting refers to a surgical procedure to move tissue from one site to another on the body, or from another person, without bringing its own blood supply with it. Instead, a new blood supply grows in after it is placed. A similar technique where tissue is transferred with the blood supply intact...
and patient survival in renal transplant recipients with sickle nephropathy is diminished as compared to those with other causes of end-stage renal disease.