Metabolic Pathways

Metabolic pathways are series of chemical reactions which take place within a cell. In each metabolic pathway, a principal chemical is modified by chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function properly. Because of the many chemicals that may be involved, metabolic pathways can be quite elaborate. In addition, many pathways can exist within a cell. This collection of pathways is called the metabolic network. Pathways are important to the maintenance of homeostasis within an organism.

There is a very large number of metabolic pathways. In humans, the most important metabolic pathways are:

1) glycolysis, which is glucose oxidation in order to obtain Adenosine triphosphate (ATP); 2) citric acid cycle (Krebs' cycle), which is acetyl-CoA oxidation in order to obtain GTP and valuable intermediates; 3) oxidative phosphorylation, which is the disposal of the electrons released by glycolysis and citric acid cycle; 4) pentose phosphate pathway, which is the synthesis of pentoses and release of the reducing power needed for anabolic reactions; 5) urea cycle, which is the disposal of NH4+ in less toxic forms; 6) fatty acid b-oxidation, which is the breakdown of fatty acids into acetyl-CoA, to be used by the Krebs' cycle; 7) gluconeogenesis, which is glucose synthesis from smaller percursors, to be used by the brain.

Oxidative Phosphorylation

Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate (ATP). Although the many forms of life on earth use a range of different nutrients, almost all carry out oxidative phosphorylation to produce ATP, which is the molecule that supplies energy to metabolism. This pathway is probably so pervasive because it is a highly efficient way of releasing energy, compared to alternative fermentation processes such as anaerobic glycolysis.

During oxidative phosphorylation, electrons are transferred from electron donors to electron acceptors such as oxygen, in redox reactions. These redox reactions release energy, which is used to form ATP. In eukaryotes, these redox reactions are carried out by a series of protein complexes within mitochondria, whereas, in prokaryotes, these proteins are located in the cells' inner membranes. These linked sets of enzymes are called electron transport chains. In eukaryotes, five main protein complexes are involved, whereas in prokaryotes many different enzymes are present, using a variety of electron donors and acceptors.

The energy released by electrons flowing through this electron transport chain is used to transport protons across the inner mitochondrial membrane, in a process called chemiosmosis. This generates potential energy in the form of a pH gradient and an electrical potential across this membrane. This store of energy is tapped by allowing protons to flow back across the membrane and down this gradient, through a large enzyme called ATP synthase. This enzyme uses this energy to generate ATP from adenosine diphosphate (ADP), in a phosphorylation reaction. This reaction is driven by the proton flow, which forces the rotation of a part of the enzyme; the ATP synthase is a rotary mechanical motor.

Although oxidative phosphorylation is a vital part of metabolism, it produces reactive oxygen species such as superoxide and hydrogen peroxide, which lead to propagation of free radicals, damaging cells and contributing to disease and, possibly, aging (senescence). The enzymes carrying out this metabolic pathway are also the target of many drugs and poisons that inhibit their activities.

Oxidative Phosphorylation Explained by a Professor (Video)

Phosphorylation

Phosphorylation is a quimical process which consists of the addition of a phosphate (PO4) group to a protein or other organic molecule such as glucose. Phosphorylation also involves the addition of phosphate to glucose to produce glucose monophosphate. Phosphorylation activates or deactivates many protein enzymes, causing or preventing the mechanisms of diseases such as cancer and diabetes.

Protein phosphorylation in particular plays a significant role in a wide range of cellular processes. Its prominent role in biochemistry is the subject of a very large body of research. Phosphorylation is carried out through the action of enzymes known as phosphotransferases or kinases.

Acute Kidney Injury

Acute kidney injury (AKI), also known as acute renal failure, is a rapidly progressive loss of renal function, which is characterized by oliguria (decreased urine production, quantified as less than 400 mL per day in adults, less than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); body water and body fluids disturbances; and electrolyte derangement. AKI can result from a variety of causes, generally classified as prerenal, intrinsic, and postrenal. An underlying cause must be identified and treated to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these fundamental causes.

Acute kidney injury can be caused by damage to the glomeruli, renal tubules, or interstitium. Common causes of each are glomerulonephritis, acute tubular necrosis (ATN), and acute interstitial nephritis (AIN), respectively. Other causes of acute kidney injury can be decrease effective blood flow to the kidney. These include low blood volume, low blood pressure, and heart failure. Changes to the blood vessels supplying the kidney can also lead to prerenal AKI. These include renal artery stenosis, which is a narrowing of the renal artery that supplies the kidney, and renal vein thrombosis, which is the formation of a blood clot in the renal vein that drains blood from the kidney.

The treatment of acute kidney injury is the treatment of the underlying cause of this condition. In addition to treatment of the underlying disorder, management of AKI routinely includes the avoidance of substances that are toxic to the kidneys, called nephrotoxins. These include NSAIDs such as ibuprofen, iodinated contrasts such as those used for CT scans, and others. Monitoring of renal function, by serial serum creatinine measurements and monitoring of urine output, is routinely performed. In the hospital, insertion of a urinary catheter helps monitor urine output and relieves possible bladder outlet obstruction, such as with an enlarged prostate.

Kidney Failure

kidney failure is a medical condition in which the kidneys fail to function properly. There are two forms of kidney failure: acute (acute kidney injury) and chronic (chronic kidney disease); either form may be due to a large number of other medical problems.

Kidney failure is detected by an elevated serum creatinine. When renal failure occurs, there is a decrease in the glomerular filtration rate. When the kidneys does not function adequately, there are abnormal fluid levels in the body, deranged acid levels, abnormal levels of potassium, calcium, phosphate, hematuria (blood in the urine) and (in the longer term) anemia. Long-term kidney problems have significant repercussions on other diseases, such as cardiovascular disease.

cystitis

Cystitis is inflammation of the urethra and bladder. Most of the time, the inflammation is caused by a bacterial infection, in which case it can also be referred to as a urinary tract infection. A bladder infection is painful and irritating, and can become a serious health problem if the infection spreads to your kidneys.

Cystitis occurs when the urethra and bladder, which make up the lower urinary tract, is infected by bacteria and becomes irritated and inflamed. The condition frequently affects sexually active women ages 20 to 50 but may also occur in those who are not sexually active or in young girls. Older adults are also at high risk for developing cystitis, with the incidence in the elderly being much higher than in younger people. In women the most common cause of infection is from E. coli and Staphylococcus saprophyticus.

Cystitis is rare in males. Females are more prone to the development of cystitis because of their shorter urethra — bacteria do not have to travel a long way to enter the bladder— and because of the relatively short distance between the opening of the urethra and the anus. Nevertheless, it is not an exclusively female disease.

The symptoms of cystitis are: 1) painful urination (dysuria); 2) urgent need to urinate (urinary urgency); 3) abnormal urine color (cloudy), similar to a urinary tract infection; 4) foul or strong urine odor; 5) blood in the urine (hematuria).

A urinalysis commonly reveals white blood cells (WBCs) or red blood cells (RBCs). A urine culture (clean catch) or catheterized urine specimen may be performed to determine the type of bacteria in the urine and the appropriate antibiotic for treatment. Prompt treatment is almost always recommended due to the risk of the infection spreading to the kidneys. It is advised to avoid vaginal penetration until the infection has cleared up. Antibiotics are used to control bacterial infection. It is vital that a course of antibiotics, once started, be completed.

Cystitis may also occur as a reaction to certain drugs, radiation therapy or potential irritants, such as feminine hygiene spray, spermicidal jellies or long-term use of a catheter. Cystitis may also occur as a complication of another illness.

Diabetic Nephropathy

Diabetic nephropathy is nephropathy caused by diabetes. In severe cases it leads to kidney failure. Also known as Kimmelstiel-Wilson syndrome, diabetic nephropathy is caused by angiopathy of capillaries in the kidney glomeruli. This means that excesive sugar in the blood for a long period of time can destroy the kidney nephrons glomeruli. It involves nephrotic syndrome and diffuse glomerulosclerosis. It is caused by longstanding diabetes mellitus, and is a prime indication for dialysis in many Western countries.

The diabetic nephropathy can be seen in patients with chronic diabetes, so patients are usually of older age (between 50 and 70 years old). The disease is progressive and may cause death two or three years after the initial lesions, and is more frequent in men. Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage kidney disease in the United States. As diabetic nephropathy progresses, increasing numbers of glomeruli are destroyed by nodular glomerulosclerosis. Now the amounts of albumin being excreted in the urine increases, and may be detected by ordinary urinalysis techniques. At this stage, a kidney biopsy clearly shows diabetic nephropathy.

In the first stages of diabetic nephropathy there are no symptoms. That is why it is important to have regular urine tests to find kidney damage early. Sometimes early kidney damage can be reversed, but not always. The first sign of kidney damage is a small amount of protein in the urine, which is found by a simple urine test.

Nephropathy

Nephropathy means a damage to or disease of the kidney. Nephrosis is an older term for nephropathy. Causes of nephropathy include administration of analgesics, which triggers analgesics nephropathy, xanthine oxidase deficiency, and long-term exposure to lead or its salts. Chronic conditions that can produce nephropathy include systemic lupus erythematosus, diabetes mellitus and high blood pressure (hypertension), which lead to diabetic nephropathy and hypertensive nephropathy, respectively.

Prostatitis

Prostatitis is an inflammation of the prostate gland, in men. Prostatitis is a painful condition that affects mostly young and middle-aged men. Prostatitis means, in its strictest sense, to histological (microscopic) inflammation of the tissue of the prostate gland, although it is loosely (and confusingly) used to describe several completely different conditions.

There are two types of prostatitis: 1) acute prostatitis, which is a bacterial infection of the prostate gland that requires urgent medical treatment; 2) chronic bacterial prostatitis, which is a rare condition that usually presents as intermittent urinary tract infections.

Dysuria

In urology, dysuria is difficult or painful urination. Usually, dysuria is a symptom caused by bacterial infection of the urinary tract. It is commonly described as a burning or stinging sensation. It is most often a result of a urinary tract infection. It may also be due to an STD, bladder stones, bladder tumours, and virtually any condition of the prostate.

Minimal Change Disease

Minimal change disease, also called nil disease, is a renal disorder in which the glomeruli of the kidney are damaged, causing nephrotic syndrome in children. Although minimal change disease mostly affects children, it is also frequently seen in adults.

It is by far the most common cause of nephrotic syndrome (NS) in children under 10 years of age, accounting for the majority (about 90%) of these diagnoses. Among teenagers who develop NS, it is caused by minimal change disease about half the time. It can also occur in adults but accounts for less than 20% of adults diagnosed with NS. Among children less than 10 years of age, boys seem to be more likely to develop minimal change disease than girls.

Although the cause is unknown, the disease can occur after allergic reactions and viral infection. The symptoms are proteinuria (leakage of protein into the urine) and edema (water retention). When viewed with an electron microscope, it discloses diffuse loss of podocytes. Nevertheless, the appearance is normal using optical microscope.

To treat minimal change disease, prednisone is prescribed along with a blood pressure medication, typically an ACE inhibitor such as lisinopril. Some nephrologists will start out with the ACE inhibitor first in an attempt to reduce the blood pressure's force which pushes the protein through the cell wall in order to lower the proteinuria.

Epithelial Cell Casts

Epithelial casts are formed by adhesion of desquamated dead epithelial cells of the renal tubule lining. Epithelial cells can adhere in random order or in sheets and are distinguished by large, round nuclei and a lower amount of cytoplasm. Epithelial cell casts reflect damage to the renal tubules and can be seen in acute tubular necrosis and toxic ingestion, such as from mercury, diethylene glycol, or salicylate. In each case, clumps or sheets of cells may slough off simultaneously, depending of the focality of injury. Cytomegalovirus and viral hepatitis are organisms that can cause epithelial cell death as well.

Epithelial casts, or cellular casts, are found in urine when renal diseases, such as ischemic acute tubular necrosis, infarction, or nephrotoxicity, cause degeneration and necrosis of tubular epithelial cells. The presence of these casts indicates acute tubular injury but does not indicate the extent or reversibility of the injury. A common scenario is the patient with decreased renal perfusion and oliguria secondary to severe dehydration. Ischemic injury results in degeneration and sloughing of the epithelial cells.

Epithelial casts

Acute Tubular Necrosis

Acute tubular necrosis (ATN) is a renal desorder which consists of the death of tubular cells. It is caused by lack of oxygen or by toxic drug exposure. Tubular cells form the renal tubules of the nephrons of the kidney, and they continually replace themselves; so, if the cause of acute tubular necrosis is removed then recovery is likely. ATN usually results in acute renal failure (ARF). The presence of brown epithelial casts in the urine during urinalysis is pathognomonic for ATN.

Acute tubular necrosis can be classified as either toxic or ischemic. Ischemic ATN occurs when the tubular cells do not get enough oxygen, a condition that they are highly sensitive and susceptible to, due to their very high metabolism. Toxic ATN occurs when the tubular cells are exposed to a toxic substance (nephrotoxic ATN). Toxic acute tubular necrosis is characterized by proximal tubular epithelium necrosis due to toxic substances, such as poisons, organic solvents, or drugs. Necrotic cells fall into the tubule lumen, obliterating it, and determining acute renal failure.

There are medical and surgical situations which are associated with a high risk for developing ischemic acute tubular necrosis: 1) infection in the blood or tissues; 2)hypotension; 3) obstructive jaundice; 4) open heart surgery, or repair of abdominal aortic aneurysm.

Renal Hypertension

Renal hypertension is a disease which envolves high blood pressure caused by narrowing of the arteries supplying the kidneys. It is a form of secondary hypertension - a form of hypertension whose cause is identifiable.

When the arteries that carry blood to your kidneys become narrow or partially blocked, less blood flows to the kidneys. The kidneys mistakenly respond as if your blood pressure is low and give off hormones that tell the body to hold on to more salt and water. This causes your blood pressure to rise.

Renal hypertension can be diagnosed using digital image processing of radiographs. Treatment may involve angioplasty, which is the mechanically widening of a blood vessel, and stenting of the renal arteries. Renal hypertension may be related to other diseases of the epithelium.

Renal Papillary Necrosis

Renal papillary necrosis is a form of nephropathy which is characterized by necrosis of the renal papillae, which is is the area where the openings of the collecting ducts enter the kidney.

Renal papillary necrosis can be caused by analgesic nephropathy. The damage is cumulative and most patients of renal papillary necrosis would have ingested at least 20kg of analgesics in the past. The risk is higher for phenacetin and acetaminophen compared to aspirin and other NSAIDs. Combination analgesic products, such as Goody's, also have a high risk of causing papillary necrosis.

Renal papillary necrosis is also caused by diabetes mellitus and vaso-occlusive sickle cell crisises, in which it is related to renal infection or vascular disease. It can also occur as a result of acute pyelonephritis.

Treatment for renal papillary necrosis depends on the underlying cause. For example, if analgesic nephropathy is suspected as the cause, your doctor will recommend that you stop using the suspected medications. This may allow healing over time.

Renal Papilla

The renal papilla is a blunted apex that projects into the renal pelvis through which the collecting tubules discharge. It is the location where the Medullary pyramids empty urine into the renal pelvis. Histologically, the renal papilla is marked by medullary collecting ducts converging to channel the fluid. Transitional epithelium begins to be seen.

Damage to the renal papillae may result in death to cells in this region of the kidney, called renal papillary necrosis.

Nephrectomy

Nephrectomy is the removal of one or both kidneys by means of a surgical procedure. The first successful nephrectomy was carried out by the German surgeon Gustav Simon on August 2, 1869, in Heidelberg, Germany, proving that one healthy kidney can be sufficient for urine excretion in humans. Simon had practiced the operation in animal experiments.

Nephrectomy has a simple and a radical approach. A simple nephrectomy is performed on patients with irreversible kidney damage because of severe traumatic injury, symptomatic chronic infection, and obstruction. Simple nephrectomy is also carried out to treat renovascular hypertension due to noncorrectable renal artery disease or severe unilateral parenchymal damage caused by nephrosclerosis, pyelonephritis, reflux dysplasia, or congenital dysplasia of the kidney. Radical nephrectomy is used for localized renal cell carcinoma. Radical nephrectomy is also indicated to treat locally advanced RCC and metastatic RCC.

To perform the surgery the patient must be under general anesthesia. Then, the surgeon makes an incision in the side of the abdomen to reach the kidney. Depending on circumstances, the incision can also be made midline. The ureter and blood vessels are disconnected, and the kidney is then removed. The surgery can be done as open surgery, with one incision, or as a laparoscopic procedure, with three or four small cuts in the abdominal and flank area. Recently, this procedure is performed through a single incision in the patient's belly-button. This advanced technique is called as Single Port Access Surgery.

Analgesic Nephropathy

Analgesic nephropathy is a medical condition in which the kidney does not function properly, with impaired filtering capacity, due to an excessive ingestion of analgesic medications such as aspirin, nimesulide, phenacetin, and paracetamol. Analgesic nephropathy usually refers to damage induced by excessive use of combinations of these medications, especially combinations that include phenacetin, gradually leading to irreversible kidney failure and the permanent need for dialysis or a kidney transplant to restore kidney function. It may also be used to describe kidney injury from any single analgesic medication.

The kidney damage produced by analgesics are renal papillary necrosis and chronic interstitial nephritis. They appear to result from decreased blood flow to the kidney, rapid consumption of antioxidants, and subsequent oxidative damage to the kidney. This kidney damage may lead to abnormal urinalysis results, high blood pressure, and anemia. A small proportion of individuals with analgesic nephropathy may develop end-stage kidney disease.

Analgesic nephropathy was once a common cause of kidney injury and end-stage kidney disease in parts of Europe, Australia, and the United States. The scarring of the small blood vessels, called capillary sclerosis, is the initial lesion of analgesic nephropathy. Found in the renal pelvis, ureter, and capillaries supplying the nephrons, capillary sclerosis is thought to lead to renal papillary necrosis and, in turn, chronic interstitial nephritis. How phenacetin and other analgesics lead to this damage is incompletely understood. It is currently thought that the renal toxicities of NSAIDs and the antipyretics phenacetin and paracetamol may combine to give rise to analgesic nephropathy. A committee of investigators reported in 2000 that there was insufficient evidence to suggest that non-phenacetin analgesics by themselves are associated with analgesic nephropathy.

If someone has been taking analgesics regularly to control chronic pain, he may be advised to find new ways to treat his pain, such as behavior modification or relaxation techniques. Depending on how much his kidney function has declined, he may be advised to change his diet, limit the fluids he drinks, or take medications to avoid anemia and bone problems caused by kidney disease. His doctor will monitor his kidney function with regular urine and blood tests.

Polycystic Kidney Syndrome

Polycystic kidney syndrome is identified by the presence of multiple cysts in both kidneys. It is a genetic disorder of the kidneys which is passed down from one generation to the next as an autosomal dominant trait and results from mutations in either the PKD-1 or PKD-2 gene. If one parent carries the gene, the offspring has a 50% chance of developing the disorder. The cysts are non-cancerous and look like sacs containing water-like fluid.

The cysts are numerous and are filled with fluids which enlarge the kidneys. The disease can also damage the liver, pancreas, and in some rare cases, the heart and brain. The two major forms of polycystic kidney disease are distinguished by their patterns of inheritance.

Polycystic kidney syndrome is the most common genetic, life threatening disease affecting more than 600,000 Americans and an estimated 12.5 million people worldwide. The PKD Foundation is the only organization worldwide dedicated to fighting polycystic kidney disease. The one of the risks for patients suffering from polycystic kidney syndrome is developing high blood pressure. Kidney failure is another common problem for people with polycystic kidney disease.

Polycystic kidney syndrome is also known as polycystic kindney disease, whose symptoms include: high blood pressure, blood in your urine, back or side pain related to enlarged kidneys, kidney stones, headache, frequent urination, increase in the size of your abdomen.

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. Nephrotic syndrome can be triggered by various disorders which damage the kidneys, particularly the basement membrane of the glomerulus, and when the basement membrane is damaged, there is abnormal excretion of protein in the urine. The most common cause of nephrotic syndrome in children is minimal change disease, and in adults the main cause is membranous glomerulonephritis.

Kidneys affected by nephrotic syndrome have small pores in the podocytes, large enough to permit proteinuria (and subsequently hypoalbuminemia, because some of the protein albumin has gone from the blood to the urine) but not large enough to allow cells through (hence no hematuria). By contrast, in nephritic syndrome, RBCs pass through the pores, causing hematuria.

Nephrotic syndrome also occurs as a result of infection, such as strep throat, hepatitis, or mononucleosis, use of certain drugs, cancer, genetic disorders, immune disorders, or diseases that affect multiple body systems including diabetes, systemic lupus erythematosus, multiple myeloma, and amyloidosis. swelling is the most common symptom, specially in the feet and ankles. Other symptons are weight gain from fluid retention, foamy appearance of the urine, high blood pressure, poor appetite.

Glomerulosclerosis

Glomerulosclerosis is a renal condition in which the glomerulus (glomeruli) of the kidney hardens due to scarring. The kidneys' tiny blood vessels, called glomeruli, become scarred, altering the filtering capacity of the kidneys and allowing protein to leak from the blood into urine.

One of the signs of glomerulosclerosis is proteinuria, which is the loss of protein in the urine. A kidney biopsy may be necessary to determine whether a patient has glomerulosclerosis or another kidney problem. Around 15% of patients with proteinuria turn out to have glomerulosclerosis. One type of glomerulosclerosis is triggered by diabetes. Drug use or infections may cause focal segmental glomerulosclerosis (FSGS), a very chronic kidney condition. FSGS may also occur in patients with AIDS but most are of unknown cause.

Because scarred glomeruli cannot be repaired, most patients with glomerulosclerosis get worse over time until their kidneys stop functioning. This condition is called end-stage renal disease and the patients must begin dialysis treatment or endure a kidney transplant. ESRD may be reached within a year or up to ten or more of diagnosis of glomerulosclerosis but time will vary. Treatments for glomerulosclerosis depend on what caused the scarring of the glomeruli. This is determined by renal biopsy. Immunosuppressants, drugs that suppress the immune system, stop proteinuria in some patients, but once the treatments have ended proteinuria will continue. The drugs may sometimes hurt the patient’s kidneys even more.

Wegener's Granulomatosis

Wegener's granulomatosis is a disease in which blood vessels get inflamed and blood does not flow well, as it should. This rare medical condition is a type of vasculitis that affects the kidneys and other organs. Due to its end-organ damage, Wegemer's granulomatosis can be a serious and requires long-term immunosuppression. The disease is named for Dr. Friedrich Wegener, who described the malady in 1936.

The cause of Wegener's granulomatosis is not known yet. It could be an autoimmune disorder. It is most common in middle-aged adults. Wegener's granulomatosis is part of a larger group of vasculitic syndromes, all of which feature the presence of an abnormal type of circulating antibody termed ANCAs (antineutrophil cytoplasmic antibodies) and affect small and medium-size blood vessels.

The first symptoms of Wegener's granulomatosis varies widely. So, diagnosis can sometimes be severely delayed becauses of the nonspecific nature of the symptoms. Rhinitis is generally the first sign in most patients. Upper airway, eye and ear disease. Nose: pain in the nose, stuffiness, nosebleeds, rhinitis, crusting, saddle-nose deformity due to a perforated septum; ear: conductive hearing loss due to auditory tube dysfunction, sensorineural hearing loss (unclear mechanism); strawberry gingivitis, underlying bone destruction with loosening of teeth, non-specific ulcerations throughout oral mucosa; eyes: pseudotumours, scleritis, conjunctivitis, uveitis, episcleritis.

But the disease becomes dangerous when it affects the kidney and lungs. The renal symptom of the Wegener's granulomatosis is rapidly progressive glomerulonephritis (75%), which leads to chronic renal failure. The lungs develop pulmonary nodules, which are often referred to as "coin lesions", infiltrates, which are often interpreted as pneumonia, cavitary lesions, pulmonary hemorrhage causing hemoptysis, and rarely bronchial stenosis.

Treatment for Wegener's granulomatosis

Before steroid treatment became available, mortality within one year was over 90%, with average survival being 5 months. Steroids prolonged average survival to 8 months. The introduction of cyclophosphamide (CYC) in the 1970s was a major breakthrough. Initial treatment is generally with corticosteroids and oral CYC, 1 mg/kg/day and 2 mg/kg/day, respectively. Occasionally CYC is given in monthly intravenous (IV) doses. Monitoring of the white blood count is essential during CYC therapy. Once remission is attained (normally 3 to 6 months), treatment is frequently changed to azathioprine or methotrexate, which are less toxic drugs. Total duration of therapy should be at least one year, or longer in high risk patients. Corticosteroids are tapered to a low maintenance dose, 5–10 mg/day. Plasmapheresis may be beneficial in severe disease or pulmonary hemorrhage.

Dialysis

Dialysis is a man-made ultrafiltration system which works as an artificial replacement for lost kidney function due to renal failure. Dialysis can be used for very sick patients with acute renal failure (patients who have suddenly but temporarily, lost their kidney function), or for quite stable patients who have permanently lost their kidney function (stage 5 chronic kidney disease). For patients with stage 5, or End-Stage Kidney Disease (ESKD), the decline in kidney function occurred over a period of months to years until a level was reached at which treatment was needed for survival. The treatment for estage 5 chronic kidney disease that most naturally replaces lost kidney function is a kidney transplant.

Dialysis works on the principles of the diffusion of solutes and ultrafiltration of fluid across a semi-permeable membrane. Diffusion describes a property of substances in water. Substances in water tend to move from an area where they are in a high concentration to an area of low concentration. Blood flows by one side of a semi-permeable membrane, and a dialysate, or special dialysis fluid, flows by the opposite side. A semipermeable membrane is a thin layer of material that contains various sized holes, or pores. Smaller solutes and fluid pass through the membrane, but the membrane blocks the passage of larger substances (for example, red blood cells, large proteins).

The two main types of dialysis, Hemodialysis (HD) and Peritoneal Dialysis (PD), remove wastes and excess water from the blood in different ways. Hemodialysis removes wastes and water by circulating blood outside the body through an external filter, called a dialyzer, that contains a semipermeable membrane. In hemodialysis, the patient's blood is pumped through the blood compartment of a dialyzer, exposing it to a partially permeable membrane. The dialyzer consists of thousands of tiny synthetic hollow fibers. The fiber wall acts as the semipermeable membrane. Blood flows through the fibers, dialysis solution flows around outside the fibers, and water and wastes move between these two solutions. The cleansed blood is then returned via the circuit back to the body. Ultrafiltration occurs by increasing the hydrostatic pressure across the dialyzer membrane.

Peritoneal dialysis is a sterile solution which contains minerals and glucose. This solution is run through a tube into the peritoneal cavity, the abdominal body cavity around the intestine, where the peritoneal membrane acts as a semipermeable membrane.The peritoneal membrane or peritoneum is a layer of tissue containing blood vessels that lines and surrounds the peritoneal, or abdominal, cavity and the internal abdominal organs (stomach, spleen, liver, and intestines). The dialysate is left there for a period of time to absorb waste products, and then it is drained out through the tube and discarded. This cycle or "exchange" is normally repeated 4-5 times during the day, (sometimes more often overnight with an automated system). Ultrafiltration occurs via osmosis; the dialysis solution used contains a high concentration of glucose, and the resulting osmotic pressure causes fluid to move from the blood into the dialysate. As a result, more fluid is drained than was instilled. Peritoneal dialysis is less efficient than hemodialysis, but because it is carried out for a longer period of time the net effect in terms of removal of waste products and of salt and water are similar to hemodialysis. Peritoneal dialysis is carried out at home by the patient. Although support is helpful, it is not essential. It does free patients from the routine of having to go to a dialysis clinic on a fixed schedule multiple times per week.

Renal Tubular Acidosis

Renal tubular acidosis (RTA) is a renal disease which involves an accumulation of acid in the body because the kidneys can not appropriately excrete acids into the urine, causing a person’s blood to remain too acidic. When blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder as urine. The metabolic acidosis that results from renal tubular acidosis may be caused either by failure to recover sufficient (alkaline) bicarbonate ions from the filtrate in the proximal tubule, or by insufficient secretion of (acid) hydrogen ions into the latter portions of the nephron (distal tubule).

Although a metabolic acidosis also occurs in those with renal insufficiency, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. There are several different types of renal tubular acidosis, which all have different syndromes and different causes.

The process of breaking down food into energy generates acids. The kidneys eliminate these acids from the blood, excreting them in the urine. This function is predominantly performed by the kidney tubules. In renal tubular acidosis, the ability of the kidneys to excrete acids is partially impaired, and acid levels build up in the blood (metabolic acidosis). The balance of electrolytes is also affected. Renal tubular acidosis usually leads to these problems: calcium deposits in the kidneys, which can lead to kidney stones; low or high potassium levels in the blood; painful softening and bending of the bones; dehydration.

Healthy kidneys keep acid-base balance by excreting acids into the urine and returning bicarbonate—an alkaline, or base, substance—to the blood. This reclaimed bicarbonate neutralizes much of the acid that is created when food is broken down in the body. The movement of substances like bicarbonate between the blood and structures in the kidneys is called transport.

Distal renal tubular acidosis (dRTA) is the most commun form of RTA. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3.

Renal tubular acidosis treatment consists of a correction of the acidemia with oral sodium bicarbonate or sodium citrate. This will correct the acidemia and reverse bone demineralisation. Hypokalemia and urinary stone formation and nephrocalcinosis can be treated with potassium citrate tablets which not only replace potassium but also inhibit calcium excretion and thus do not exacerbate stone disease as sodium bicarbonate or citrate may do.

Fanconi Syndrome

The Fanconi syndrome is a renal disorder in which the proximal tubules function is impaired, which results in decreased reabsorption of electrolytes and nutrients back into the bloodstream. These nutrients and electrolytes are released into the urine instead. These released compounds include glucose, amino acids, uric acid, phosphate and bicarbonate. Although the cause of Falconi syndrome is unkown, it may be caused by faulty genes, or it may result later in life due to kidney damage.

The reduced reabsorption of bicarbonate results in Type 2 or Proximal renal tubular acidosis, which may in some cases exist on its own, or more usually in combination with the Fanconi syndrome. Common causes of Fanconi syndrome in children are genetic defects that affect the body's ability to break down certain compounds such as: cystine, fructose, galactose, glycogen. Cystinosis is the most common cause of Fanconi syndrome in children.

The Fanconi syndrome is named after Guido Fanconi, a Swiss pediatrician.