A urinalysis will typically show a decreased urine sodium level, a high urine creatinine-to-serum creatinine ratio, a high urine urea-to-serum urea ratio, and concentrated urine (determined by osmolality and specific gravity). None of these is particularly useful in diagnosis.

In pre-renal and post-renal azotemias, elevation of the BUN exceeds that of the creatinine (i.e., BUN>12*creatinine). This is because BUN is readily absorbed while creatinine is not. In congestive heart failure (a cause of pre-renal azotemia) or any other condition that causes poor perfusion of kidneys, the sluggish flow of glomerular filtrate results in excessive absorption of BUN and elevation of its value in blood. Creatinine, however, is not absorbable and therefore does not rise significantly. Stasis of urine in post-renal azotemia has the same effect.

Azotemia has three classifications, depending on its causative origin. A BUN/Cr > 20 tends to herald prerenal azotemia (commonly secondary to dehydration but also any other reason perfusion to kidneys is decreased). The BUN-to-creatinine ratio (BUN:Cr) is a useful measure in determining the type of azotemia. A normal BUN:Cr is equal to 15.

Classical signs of uremia are: progressive weakness and easy fatigue, loss of appetite due to nausea and vomiting, muscle atrophy, tremors, abnormal mental function, frequent shallow respiration and metabolic acidosis. Without intervention via dialysis or kidney transplant, uremia due to renal failure will progress and cause stupor, coma and death. Because uremia is mostly a consequence of kidney failure, its signs and symptoms often occur concomitantly with other signs and symptoms of kidney failure. Below is a table showing more of the principal signs and symptoms of uremia.

Glomerular filtration rate (GFR) measures the amount of plasma being filtered through the kidneys. As the GFR decreases, the prognosis worsens. Some of the effects can be reversed with dialysis. See below for a chart on GFR rates and their effects.

People on dialysis acquire what is known as "residual syndrome". Residual syndrome is a non-life-threatening disease which is displayed as toxic effects causing many of the same signs and symptoms that uremia displays. There are several hypotheses why residual syndrome is present. They are: (1) the accumulation of large molecular weight solutes that are poorly dialyzed (e.g. β-Microglobulin), (2) the accumulation of protein-bound small molecular weight solutes that are poorly dialyzed (e.g. "p"-cresyl sulfate and indoxyl sulfate), (3) accumulation of dialyzable solutes that are incompletely removed (e.g. sequestered solutes like phosphate in cells or insufficient elimination of other more toxic solutes), (4) indirect phenomena such as carbamylation of proteins, tissue calcification, or a toxic effect of hormone imbalance (e.g. Parathyroid hormone) and (5) the toxic effect by dialysis itself (e.g. removal of unknown important vitamins or minerals). Dialysis increases life span but patients may have more limited function. They gain physical limitations which include impairment of balance, walking speed and sensory functions. They also retain cognitive impairment such as impairment in attention, memory and performance of higher-order tasks. Patients have been maintained longer than three decades on dialysis, but unfortunately average mortality rates and hospitalizations are high. Also patient rehabilitation and quality of life is poor.

Symptoms can vary from person to person. Someone in early stage kidney disease may not feel sick or notice symptoms as they occur. When kidneys fail to filter properly, waste accumulates in the blood and the body, a condition called azotemia. Very low levels of azotaemia may produce few, if any, symptoms. If the disease progresses, symptoms become noticeable (if the failure is of sufficient degree to cause symptoms). Kidney failure accompanied by noticeable symptoms is termed uraemia.

Symptoms of kidney failure include the following:

- High levels of urea in the blood, which can result in:

- Vomiting or diarrhea (or both) which may lead to dehydration

- Nausea

- Weight loss

- Nocturnal urination

- More frequent urination, or in greater amounts than usual, with pale urine

- Less frequent urination, or in smaller amounts than usual, with dark coloured urine

- Blood in the urine

- Pressure, or difficulty urinating

- Unusual amounts of urination, usually in large quantities

- A buildup of phosphates in the blood that diseased kidneys cannot filter out may cause:

- Itching

- Bone damage

- Nonunion in broken bones

- Muscle cramps (caused by low levels of calcium which can be associated with hyperphosphatemia)

- A buildup of potassium in the blood that diseased kidneys cannot filter out (called hyperkalemia) may cause:

- Abnormal heart rhythms

- Muscle paralysis

- Failure of kidneys to remove excess fluid may cause:

- Swelling of the legs, ankles, feet, face, or hands

- Shortness of breath due to extra fluid on the lungs (may also be caused by anemia)

- Polycystic kidney disease, which causes large, fluid-filled cysts on the kidneys and sometimes the liver, can cause:

- Pain in the back or side

- Healthy kidneys produce the hormone erythropoietin that stimulates the bone marrow to make oxygen-carrying red blood cells. As the kidneys fail, they produce less erythropoietin, resulting in decreased production of red blood cells to replace the natural breakdown of old red blood cells. As a result, the blood carries less hemoglobin, a condition known as anemia. This can result in:

- Feeling tired or weak

- Memory problems

- Difficulty concentrating

- Dizziness

- Low blood pressure

- Normally, proteins are too large to pass through the kidneys, however, they are able to pass through when the glomeruli are damaged. This does not cause symptoms until extensive kidney damage has occurred, after which symptoms include:

- Foamy or bubbly urine

- Swelling in the hands, feet, abdomen, or face

- Other symptoms include:

- Appetite loss, a bad taste in the mouth

- Difficulty sleeping

- Darkening of the skin

- Excess protein in the blood

- With high doses of penicillin, people with kidney failure may experience seizures

The clinical picture is often dominated by the underlying cause.The symptoms of acute kidney injury result from the various disturbances of kidney function that are associated with the disease. Accumulation of urea and other nitrogen-containing substances in the bloodstream lead to a number of symptoms, such as fatigue, loss of appetite, headache, nausea and vomiting. Marked increases in the potassium level can lead to abnormal heart rhythms, which can be severe and life-threatening. Fluid balance is frequently affected, though blood pressure can be high, low or normal.

Pain in the flanks may be encountered in some conditions (such as clotting of the kidneys' blood vessels or inflammation of the kidney); this is the result of stretching of the fibrous tissue capsule surrounding the kidney. If the kidney injury is the result of dehydration, there may be thirst as well as evidence of fluid depletion on physical examination. Physical examination may also provide other clues as to the underlying cause of the kidney problem, such as a rash in interstitial nephritis (or vasculitis) and a palpable bladder in obstructive nephropathy.

Acute kidney injuries can be present on top of chronic kidney disease, a condition called acute-on-chronic kidney failure (AoCRF). The acute part of AoCRF may be reversible, and the goal of treatment, as with AKI, is to return the patient to baseline kidney function, typically measured by serum creatinine. Like AKI, AoCRF can be difficult to distinguish from chronic kidney disease if the patient has not been monitored by a physician and no baseline (i.e., past) blood work is available for comparison.

Acute kidney injury is diagnosed on the basis of clinical history and laboratory data. A diagnosis is made when there is a rapid reduction in kidney function, as measured by serum creatinine, or based on a rapid reduction in urine output, termed oliguria (less than 400 mLs of urine per 24 hours).

AKI can be caused by systemic disease (such as a manifestation of an autoimmune disease, e.g. lupus nephritis), crush injury, contrast agents, some antibiotics, and more. AKI often occurs due to multiple processes. The most common cause is dehydration and sepsis combined with nephrotoxic drugs, especially following surgery or contrast agents.

The causes of acute kidney injury are commonly categorized into "prerenal", "intrinsic", and "postrenal".

CKD is initially without specific symptoms and is generally only detected as an increase in serum creatinine or protein in the urine. As the kidney function decreases:

- Blood pressure is increased due to fluid overload and production of vasoactive hormones created by the kidney via the renin-angiotensin system, increasing one's risk of developing hypertension and/or suffering from congestive heart failure.

- Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Due to its high systemic circulation, urea is excreted in eccrine sweat at high concentrations and crystallizes on skin as the sweat evaporates ("uremic frost").

- Potassium accumulates in the blood (hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias). Hyperkalemia usually does not develop until the glomerular filtration rate falls to less than 20–25 ml/min/1.73 m, at which point the kidneys have decreased ability to excrete potassium. Hyperkalemia in CKD can be exacerbated by acidemia (which leads to extracellular shift of potassium) and from lack of insulin.

- Erythropoietin synthesis is decreased causing anemia.

- Fluid volume overload symptoms may range from mild edema to life-threatening pulmonary edema.

- Hyperphosphatemia, due to reduced phosphate excretion, follows the decrease in glomerular filtration. Hyperphosphatemia is associated with increased cardiovascular risk, being a direct stimulus to vascular calcification. Moreover, circulating concentrations of fibroblast growth factor-23 (FGF-23) increase progressively as the renal capacity for phosphate excretion declines, but this adaptative response may also contribute to left ventricular hypertrophy and increased mortality in CKD patients.

- Hypocalcemia, due to 1,25 dihydroxyvitamin D deficiency (caused by stimulation of FGF-23 and reduction of renal mass), and resistance to the calcemic action of parathyroid hormone. Osteocytes are responsible for the increased production of FGF-23, which is a potent inhibitor of the enzyme 1-alpha-hydroxylase (responsible for the conversion of 25-hydroxycholecalciferol into 1,25 dihydroxyvitamin D). Later, this progresses to secondary hyperparathyroidism, renal osteodystrophy, and vascular calcification that further impairs cardiac function. An extreme consequence is the occurrence of the rare condition named calciphylaxis.

- The concept of chronic kidney disease-mineral bone disorder (CKD-MBD) currently describes a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD manifested by either "one or a combination" of: 1) abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or vitamin D metabolism; 2) abnormalities in bone turnover, mineralization, volume, linear growth, or strength (renal osteodystrophy); and 3) vascular or other soft-tissue calcification. CKD-MBD has been associated to poor hard outcomes.

- Metabolic acidosis (due to accumulation of sulfates, phosphates, uric acid etc.) may cause altered enzyme activity by excess acid acting on enzymes; and also increased excitability of cardiac and neuronal membranes by the promotion of hyperkalemia due to excess acid (acidemia). Acidosis is also due to decreased capacity to generate enough ammonia from the cells of the proximal tubule.

- Iron deficiency anemia, which increases in prevalence as kidney function decreases, is especially prevalent in those requiring haemodialysis. It is multifactoral in cause, but includes increased inflammation, reduction in erythropoietin, and hyperuricemia leading to bone marrow suppression.

People with CKD suffer from accelerated atherosclerosis and are more likely to develop cardiovascular disease than the general population. Patients afflicted with CKD and cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter.

Sexual dysfunction is very common in both men and women with CKD. A majority of men have a reduced sex drive, difficulty obtaining an erection, and reaching orgasm, and the problems get worse with age. A majority of women have trouble with sexual arousal, and painful menstruation and problems with performing and enjoying sex are common.

Chronic kidney disease (CKD) is a type of kidney disease in which there is gradual loss of kidney function over a period of months or years. Early on there are typically no symptoms. Later, leg swelling, feeling tired, vomiting, loss of appetite, or confusion may develop. Complications may include heart disease, high blood pressure, bone disease, or anemia.

Causes of chronic kidney disease include diabetes, high blood pressure, glomerulonephritis, and polycystic kidney disease. Risk factors include a family history of the condition. Diagnosis is generally by blood tests to measure the glomerular filtration rate and urine tests to measure albumin. Further tests such as an ultrasound or kidney biopsy may be done to determine the underlying cause. A number of different classification systems exist.

Screening at-risk people is recommended. Initial treatments may include medications to manage blood pressure, blood sugar, and lower cholesterol. NSAIDs should be avoided. Other recommended measures include staying active and certain dietary changes. Severe disease may require hemodialysis, peritoneal dialysis, or a kidney transplant. Treatments for anemia and bone disease may also be required.

Chronic kidney disease affected about 323 million people globally in 2015. In 2015 it resulted in 1.2 million deaths, up from 409,000 in 1990. The causes that contribute to the greatest number of deaths are high blood pressure at 550,000, followed by diabetes at 418,000, and glomerulonephritis at 238,000.

Sickle cell nephropathy is a type of nephropathy associated with sickle cell disease which causes kidney complications as a result of sickling of red blood cells in the small blood vessels. 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 glomerular 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 protein in the urine.

Mild increases in the blood levels of nitrogen and uric acid can also develop. Advanced kidney failure and high blood urea levels 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, kidney complications of sickle cell disease include cortical infarcts leading to loss of function, persistent bloody urine, 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 kidney tissues and functional tubule abnormalities. The presence of visible blood in the urine without pain 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 high blood potassium, metabolic acidosis, and a defect in uric acid excretion which, combined with increased purine synthesis in the bone marrow, results in high blood uric acid levels.

By far, the most common type of kidney stones worldwide contains calcium. For example, calcium-containing stones represent about 80% of all cases in the United States; these typically contain calcium oxalate either alone or in combination with calcium phosphate in the form of apatite or brushite. Factors that promote the precipitation of oxalate crystals in the urine, such as primary hyperoxaluria, are associated with the development of calcium oxalate stones. The formation of calcium phosphate stones is associated with conditions such as hyperparathyroidism and renal tubular acidosis.

Oxaluria is increased in patients with certain gastrointestinal disorders including inflammatory bowel disease such as Crohn disease or patients who have undergone resection of the small bowel or small bowel bypass procedures. Oxaluria is also increased in patients who consume increased amounts of oxalate (found in vegetables and nuts). Primary hyperoxaluria is a rare autosomal recessive condition which usually presents in childhood.

Calcium oxalate crystals in urine appear as 'envelopes' microscopically. They may also form 'dumbbells.'

Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder. Nephrolithiasis refers to the presence of such stones in the kidneys. Calyceal calculi are aggregations in either the minor or major calyx, parts of the kidney that pass urine into the ureter (the tube connecting the kidneys to the urinary bladder). The condition is called ureterolithiasis when a calculus is located in the ureter. Stones may also form or pass into the bladder, a condition referred to as bladder stones.

Acute uric acid nephropathy (AUAN) due to hyperuricosuria has been a dominant cause of acute kidney failure but with the advent of effective treatments for hyperuricosuria, AUAN has become a less common cause than hyperphosphatemia. Two common conditions related to excess uric acid, gout and uric acid nephrolithiasis, are not features of tumor lysis syndrome.

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication during the treatment of cancer, where large amounts of tumor cells are killed off (lysed) at the same time by the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias. In oncology and hematology, this is a potentially fatal complication, and patients at increased risk for TLS should be closely monitored before, during, and after their course of chemotherapy.

Tumor lysis syndrome is characterized by high blood potassium (hyperkalemia), high blood phosphorus (hyperphosphatemia), low blood calcium (hypocalcemia), high blood uric acid (hyperuricemia), and higher than normal levels of blood urea nitrogen (BUN) and other nitrogen-containing compounds (azotemia). These changes in blood electrolytes and metabolites are a result of the release of cellular contents of dying cells into the bloodstream from breakdown of cells. In this respect, TLS is analogous to rhabdomyolysis, with comparable mechanism and blood chemistry effects but with different cause. In TLS, the breakdown occurs after cytotoxic therapy or from cancers with high cell turnover and tumor proliferation rates. The metabolic abnormalities seen in tumor lysis syndrome can ultimately result in nausea and vomiting, but more seriously acute uric acid nephropathy, acute kidney failure, seizures, cardiac arrhythmias, and death.

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 graft and patient survival in kidney transplant recipients with sickle nephropathy is lower when compared to those with other causes of end-stage kidney disease.

Cardiorenal syndrome (CRS) is an umbrella term used in the medical field that defines disorders of the heart and kidneys whereby “acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other”. The heart and the kidneys are involved in maintaining hemodynamic stability and organ perfusion through an intricate network. These two organs communicate with one another through a variety of pathways in an interdependent relationship. In a 2004 report from National Heart, Lung and Blood Institute, CRS was defined as a condition where treatment of congestive heart failure is limited by decline in kidney function. This definition has since been challenged repeatedly but there still remains little consensus over a universally accepted definition for CRS. At a consensus conference of the Acute Dialysis Quality Initiative (ADQI), the CRS was classified into five subtypes primarily based upon the organ that initiated the insult as well as the acuity of disease.

Ronco et al. first proposed a five-part classification system for CRS in 2008 which was also accepted at ADQI consensus conference in 2010. These include:

The distinction between CRS type 2 and CRS type 4 is based on the assumption that, also in advanced and chronic disease, two different pathophysiological mechanisms can be distinguished, whereas both CKD and HF often develop due to a common pathophysiological background, most notably hypertension and diabetes mellitus. Furthermore, the feasibility of the distinction between CRS type 2 and 4 in terms of diagnosis can be questioned.

Braam et al. argue that classifying the CRS based on the order in which the organs are affected and the timeframe (acute vs chronic) is too simplistic and without a mechanistic classification it is difficult to study CRS. They view the cardiorenal syndrome in a more holistic, integrative manner. They defined the cardiorenal syndrome as a pathophysiological condition in which combined heart and kidney dysfunction amplifies progression of failure of the individual organ, by inducing similar pathophysiological mechanisms. Therefore, regardless of which organ fails first, the same neurohormonal systems are activated causing accelerated cardiovascular disease, and progression of damage and failure of both organs. These systems are broken down into two broad categories of "hemodynamic factors" and non-hemodynamic factors or "cardiorenal connectors".

If hyponatremia (low sodium) and hyperkalemia (high potassium) are severe, the resulting hypovolemia, prerenal azotemia, and cardiac arrhythmias may result in an Addisonian crisis. In severe cases, the patient may be presented in shock and moribund. Addisonian crisis must be differentiated from other life-threatening disorders such as diabetic ketoacidosis, necrotizing pancreatitis, and septic peritonitis.

The most common clinical manifestations are related to mental status and gastrointestinal function; they include lethargy, anorexia, vomiting, weight loss, and weakness. Additional findings may include dehydration, bradycardia, weak femoral pulses, and abdominal pain. Polyuria and polydipsia, diarrhea, and shivering are occasionally reported.

Symptoms of hypoadrenocorticism can include vomiting, diarrhea, lethargy, lack of appetite, tremors or shaking, muscle weakness, low body temperature, collapse, low heart rate, and pain in the hind quarters. Hypoglycemia can also be present, and initially may be confused with seizure disorders, insulin-secreting pancreatic tumor (insulinoma), food poisoning, parvovirus enteritis, gastric volvulus, spinal or joint problems, earning hypoadrenocorticism the nicknames of "the Great Mimic" and "the Great Imitator". It is possible not to see any signs of the disease until 90% of the adrenal cortex is no longer functioning.

Epidemic dropsy is a form of edema of extremities due to poisoning by "Argemone mexicana" (Mexican prickly poppy).

Epidemic dropsy is a clinical state resulting from use of edible oils adulterated with "Argemone mexicana" seed oil.

Sanguinarine and dihydrosanguinarine are two major toxic alkaloids of argemone oil, which cause widespread capillary dilatation, proliferation and increased capillary permeability. When mustard oil is adulterated deliberately (as in most cases) or accidentally with argemone oil, proteinuria (specifically loss of albumin) occurs, with a resultant edema as would occur in nephrotic syndrome.

Other major symptoms are pitting edema of extremities, headache, nausea, loose bowels, erythema, glaucoma and breathlessness.

Leakage of the protein-rich plasma component into the extracellular compartment leads to the formation of edema. The haemodynamic consequences of this vascular dilatation and permeability lead to a state of relative hypovolemia with a constant stimulus for fluid and salt conservation by the kidneys. Illness begins with gastroenteric symptoms followed by cutaneous erythema and pigmentation. Respiratory symptoms such as cough, shortness of breath and orthopnoea, progressing to frank right-sided congestive cardiac failure, are seen.

Mild to moderate anaemia, hypoproteinaemia, mild to moderate renal azotemia, retinal haemorrhages, and glaucoma are common manifestations. There is no specific therapy. Removal of the adulterated oil and symptomatic treatment of congestive cardiac failure and respiratory symptoms, along with administration of antioxidants and multivitamins, remain the mainstay of treatment.

Epidemic dropsy occurs as an epidemic in places where use of mustard oil, (from the seeds of Brassica "juncea" commonly known as Indian mustard ) as cooking medium is common.

Nitric acid test and paper chromatography test are used in the detection of argemone oil.Paper chromatography test is the most sensitive test.

Diffuse scleroderma can cause musculoskeletal, pulmonary, gastrointestinal, renal and other complications. Patients with greater cutaneous involvement are more likely to have involvement of the internal tissues and organs. Most patients (over 80%) have vascular symptoms and Raynaud's phenomenon, which leads to attacks of discoloration of the hands and feet in response to cold. Raynaud's normally affects the fingers and toes. Systemic scleroderma and Raynaud's can cause painful ulcers on the fingers or toes which are known as digital ulcers. Calcinosis (deposition of calcium in lumps under the skin) is also common in systemic scleroderma, and is often seen near the elbows, knees or other joints.

- Musculoskeletal

The first joint symptoms that patients with scleroderma have are typically non specific joint pains, which can lead to arthritis, or cause discomfort in tendons or muscles. Joint mobility, especially of the small joints of the hand, may be restricted by calcinosis or skin thickening. Patients may develop muscle weakness, or myopathy, either from the disease or its treatments.

- Lungs

Some impairment in lung function is almost universally seen in patients with diffuse scleroderma on pulmonary function testing; however, it does not necessarily cause symptoms, such as shortness of breath. Some patients can develop pulmonary hypertension, or elevation in the pressures of the pulmonary arteries. This can be progressive, and can lead to right-sided heart failure. The earliest manifestation of this may be a decreased diffusion capacity on pulmonary function testing.

Other pulmonary complications in more advanced disease include aspiration pneumonia, pulmonary hemorrhage and pneumothorax.

- Digestive tract

Diffuse scleroderma can affect any part of the gastrointestinal tract. The most common manifestation in the esophagus is reflux esophagitis, which may be complicated by peptic stricturing, or benign narrowing of the esophagus. This is best initially treated with proton pump inhibitors for acid suppression, but may require bougie dilatation in the case of stricture.

Scleroderma can decrease motility anywhere in the gastrointestinal tract. The most common source of decreased motility is the esophagus and the lower esophageal sphincter, leading to dysphagia and chest pain. As scleroderma progresses, esophageal involvement from abnormalities in decreased motility may worsen due to progressive fibrosis (scarring). If this is left untreated, acid from the stomach can back up into the esophagus, causing esophagitis and GERD. Further scarring from acid damage to the lower esophagus many times leads to the development of fibrotic narrowing, also known as strictures which can be treated by dilatation, and Barrett's esophagus.

Duodenum: In patients with neuromuscular disorders, particularly progressive systemic sclerosis and visceral myopathy, the duodenum is frequently involved. There may be dilatation, which is often more pronounced in the second, third and fourth parts. The dilated duodenum may be slow to empty and the grossly dilated, atonic organ may produce a sump effect.

The small intestine can also become involved, leading to bacterial overgrowth and malabsorption of bile salts, fats, carbohydrates, proteins, and vitamins. The colon can be involved, and can cause pseudo-obstruction or ischemic colitis.

Rarer complications include pneumatosis cystoides intestinalis, or gas pockets in the bowel wall, wide mouthed diverticula in the colon and esophagus, and liver fibrosis. Patients with severe gastrointestinal involvement can become profoundly malnourished.

Scleroderma may also be associated with gastric antral vascular ectasia (GAVE), also known as "watermelon stomach". This is a condition where atypical blood vessels proliferate usually in a radially symmetric pattern around the pylorus of the stomach. GAVE can be a cause of upper gastrointestinal bleeding or iron deficiency anemia in patients with scleroderma.

- Kidneys

Renal involvement, in scleroderma, is considered a poor prognostic factor and frequently a cause of death.

The most important clinical complication of scleroderma involving the kidney is "scleroderma renal crisis". Symptoms of scleroderma renal crisis are malignant hypertension (high blood pressure with evidence of acute organ damage), hyperreninemia (high renin levels), azotemia (kidney failure with accumulation of waste products in the blood) and microangiopathic hemolytic anemia (destruction of red blood cells). Apart from the high blood pressure, hematuria (blood in the urine) and proteinuria (protein loss in the urine) may be indicative.

In the past scleroderma renal crisis was almost uniformily fatal. While outcomes have improved significantly with the use of ACE inhibitors the prognosis is often guarded, as a significant number of patients are refractory to treatment and develop renal failure. Approximately 5–10% of all diffuse cutaneous scleroderma patients develop renal crisis at some point in the course of their disease. Patients that have rapid skin involvement have the highest risk of renal complications. It is most common in diffuse cutaneous scleroderma, and is often associated with antibodies against RNA polymerase (in 59% of cases). Many proceed to dialysis, although this can be stopped within three years in about a third of cases. Higher age and (paradoxically) a lower blood pressure at presentation make it more likely that dialysis is needed.

Treatments for scleroderma renal crisis include ACE inhibitors. Prophylactic use of ACE inhibitors is currently not recommended, as recent data suggest a poorer prognosis in patient treated with these drugs prior to the development of renal crisis. Transplanted kidneys are known to be affected by scleroderma and patients with early onset renal disease (within one year of the scleroderma diagnosis) are thought to have the highest risk for recurrence.

In the skin, systemic sclerosis causes hardening and scarring. The skin may appear tight, reddish, or scaly. Blood vessels may also be more visible. Where large areas are affected, fat and muscle wastage may weaken limbs and affect appearance. Patients report severe and recurrent itching of large skin areas. The severity of these symptoms varies greatly among patients: Some having scleroderma of only a limited area of the skin (such as the fingers) and little involvement of the underlying tissue, while others have progressive skin involvement. Digital ulcers — open wounds on especially on fingertips and less commonly the knuckles — are not uncommon.

Signs include acute onset of moderate to severe pain, large volumes of gastric reflux (4–20 L per decompression) which is usually orange-brown and fetid, distended small intestine (up to 5–7 cm in diameter) palpable on rectal examination, fever, depression, increased heart rate (>60 bpm), increased respiratory rate, prolonged CRT, and darkened mucous membranes. After gastric decompression, the horse may show signs of malaise and act lethargic, but pain level usually improves.

Abdominocentesis usually reveals a yellow, turbid fluid with an increased white blood cell count (usually 5,000–10,000 cells/microliter) and protein level (>3.5 g/dl), although the fluid may be serosanginous in severe cases. A chemistry panel will often show electrolyte abnormalities (hypokalemia, hyponatremia, hypochloremia) due to electrolyte loss into the lumen of the intestine. Leukocytes may be normal, increased, or decreased. PCV and total protein are usually both increased due to fluid loss, and the horse displays a prerenal azotemia. On the chemistry panel, liver enzymes such as GGT, ALP, AST are increased, likely due to ascending infection from the common bile duct, endotoxin absorption, and hypoperfusion. A metabolic acidosis with a high anion gap is often seen due to loss of bicarbonate in gastric reflux and an increase in lactic acid in the blood, secondary to hypovolemia and decreased tissue perfusion.