الفهرس 
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Abstract
Gastrointestinal disorders and chronic kidney disease CKD is a heterogeneous group of disorders characterized by alterations in kidney structure and function, which manifest in various ways depending upon the underlying cause or causes and the severity of disease. CKD is defined by the presence of kidney damage or decreased kidney function for three or more months, irrespective of the cause. The persistence of the damage or decreased function for at least three months is necessary to distinguish CKD from acute kidney disease.
The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines have classified CKD into five stages. The U.K. National Institute of Health and Clinical Excellence (NICE) has modified, in 2008, the KDOQI CKD classification by subdividing CKD stage 3 into 3A and 3B, estimated GFR of 45 to 59 ml/min per 1.73 m2 and 30 to 44 ml/min per 1.73 m2, respectively.4 The NICE CKD guidelines also stipulated that the suffix p be added to the stages in proteinuric patients.
CKD is likely to be a multi-hit process. Risk factors for CKD include susceptibility, initiation, and progression factors. Susceptibility factors predispose to CKD, whereas initiation factors directly trigger kidney damage. Progression factors are associated with worsening of already established kidney damage. These risk factors are further classified according to feasibility for intervention as modifiable and non-modifiable. The aim of identifying susceptibility and initiation factors for CK is to define individuals at high risk for development of CKD; with progression factors, the aim is to define individuals at high risk for worsening (CKD) kidney damage and subsequent loss of kidney function.
Gastrointestinal (GI) symptoms and disease are common in patients with chronic kidney disease (CKD), including those receiving renal replacement therapy. Anorexia, nausea, and vomiting can arise from uremic toxicity. These may indicate the need to start dialysis or may be a manifestation of inadequate dialysis clearances. GI disturbances contribute to the development of malnutrition and wasting. These common complications of advanced CKD carry an adverse prognosis for survival.
Gastrointestinal diseases in chronic kidney disease include oral cavity diseases as Glossitis can result from iron, vitamin B12, or folic acid deficiency anemia. Halitosis is a feature of uremia, and reduced taste sensation or abnormal or unpleasant taste can impair dietary intake.
Dental disease may prevent adequate nutrition, gingival hyperplasia and Oral candidiasis.
Gastroesophageal Reflux Disease and Esophagitis are common complaint and defined by symptoms of heartburn or mucosal changes arising from reflux of caustic gastric contents into the esophagus. It occurs more frequently in CKD because of GI dysmotility or delayed gastric emptying and may be more prevalent in peritoneal dialysis (PD) because of increased intra-abdominal pressure.
In the early days of dialysis, peptic ulceration and GI hemorrhage were major complications of renal failure. However, with effective drug therapies and improvement in dialysis therapy, peptic ulcer disease is not more common in CKD than in the general population. Gastritis and duodenitis are common in patients with CKD and abdominal symptoms. Dyspepsia without other warning features (weight loss, vomiting, hemorrhage) may be managed by testing for H. pylori with a breath test or stool antigen test (which are valid in CKD) and an empirical course of acid-suppressing therapy.
Gastric emptying is impaired in uremia (possibly to a greater degree in PD) and is affected by some conditions leading to renal disease, particularly diabetes and amyloidosis. This results in reduced appetite, early satiety, nausea, vomiting, and malnutrition. Constipation is common in CKD. Predisposing factors include drugs, dietary restrictions, low oral fluid intake, and electrolyte abnormalities, including hypercalcemia. Pseudo-obstruction presents with acute or more chronic clinical features of abdominal pain, vomiting, constipation, or diarrhea. It arises from disordered gut motility and is more common in dysmotility states, such as diabetes, amyloidosis, and scleroderma. Drugs reducing bowel motility and electrolyte disturbance such as hypokalemia predispose to pseudo-obstruction.
Intestinal ischemia is an important cause of an acute abdomen in older CKD patients. A proportion of cases result from nonocclusive mesenteric ischemia, in which there is no critical vascular occlusion. It may be precipitated by excess fluid removal by hemodialysis (HD). Predisposing factors include hypotension, cardiac failure, hypoxia, increased plasma viscosity, and constipation. GI hemorrhage is an important complication of CKD, with increased incidence compared with the general population.
Causes include a greater incidence of lesions such as gastritis and Duodenitis, angiodysplasia, and, more rarely, dialysis related amyloidosis and systemic vasculitis. Uremic hemostatic defects and anticoagulation during HD are also important.
Clostridium difficile is a major cause of nosocomial diarrheal illness. Clinical manifestations vary from mild diarrheal illness to severe pseudo-membranous colitis (Fig. 83.4). Patients with CKD are at risk of more frequent or severe infection and have a higher resulting mortality.12 Reasons include the older age of CKD patients, frequent use of acid-suppressing drugs, and antibiotics. Diagnosis is made by identifying C. difficile toxin in diarrheal stools.
There is some evidence suggesting that acute pancreatitis is more common in CKD, and incidence may be greater in PD than in other CKD patients. Most cases are secondary to biliary tract disease or alcohol or are idiopathic. Rarer causes, in CKD patients, are hypercalcemia, vasculitis, and drugs including corticosteroids, azathioprine, angiotensin-converting enzyme (ACE) inhibitors, and diuretics. Some causes of acute abdominal pain occur more commonly in or are specific to CKD patients. A high index of suspicion for ischemic bowel is important because of the frequency of vascular disease in CKD. Pain may result from complications of autosomal polycystic kidney disease. Retroperitoneal hemorrhage can arise from anticoagulation, including during HD.
A number of conditions result in both renal and GI manifestations. These include diabetes mellitus, systemic vasculitis, systemic amyolidosis, autosomal dominant polycystic kidney disease, systemic sclerosis, inflammatory bowel disease, coeliac disease and Fabry’s disease.
Diabetes is commonly complicated by disordered gut motility. Gastroparesis needs to be distinguished from uremic upper GI symptoms. Diarrhea due to diabetic enteropathy is also common, classically is nocturnal, and usually is neurogenic in origin. Bacterial overgrowth is uncommon and is diagnosed by the hydrogen breath test. GI symptoms may be exacerbated by drug treatments for diabetes, including metformin and α-glucosidase inhibitors. Gastroparesis results in difficulties with glycemic control, fluid and electrolyte imbalance, drug malabsorption, and malnutrition. Colonic transport time is increased in diabetes, resulting in constipation.
GI manifestations of vasculitis include intestinal ischemia or infarction, hemorrhage, and perforation with peritonitis. Abnormal liver function test results arise from hepatitis, and cholecystitis and pancreatitis have been described. Serositis with abdominal pain is a feature of systemic lupus erythematosus. Abdominal pain, vomiting, and GI hemorrhage are typical of Henoch-Schonlien purpura.
Primary AL amyloidosis may result in both renal and GI involvement. Conversely, inflammatory bowel disease is an important cause of secondary AA amyloidosis, which may result in renal involvement. Thus, in a patient with renal amyloidosis who has GI symptoms, it is important to characterize the type of amyloid and the underlying cause of GI disturbance.
Abdominal hernias are more common in ADPKD14 and are a particular problem in PD patients. Colonic diverticular disease occurs more frequently. The enlarged kidneys can result in abdominal pain, hemorrhage, abdominal fullness, and anorexia. Hepatic cysts and occasionally massive hepatomegaly may cause chronic abdominal pain and fullness. Common bile duct dilation, of uncertain significance, occurs more frequently in ADPKD.
Inflammatory bowel disease may be complicated by AA amyloidosis and IgA nephropathy. Drug therapy, such as aminosalicylates, can lead to renal disease, including chronic interstitial nephritis. Terminal ileal disease in Crohn’s disease can lead to hyperoxaluria and oxalate calculi.
Celiac disease is a relatively common condition and occurs with increased frequency in association with other autoimmune conditions, such as diabetes mellitus. There is also a reported association with IgA nephropathy.
Drugs commonly used in CKD can lead to GI problems. Phosphate-binding drugs commonly result in abdominal symptoms. Nausea and vomiting are important complications of cinacalcet. Other drugs important in CKD that may cause GI problems include statins, ACE inhibitors, iron supplements, sodium bicarbonate, bisphosphonates, and metformin. Acidsuppressing drugs including proton pump inhibitors and H2 receptor blockers are commonly prescribed in CKD. They are often inappropriately continued for long periods and have their own associated side effects. They increase the risk of C. difficile infection. Proton pump inhibitors can result in symptoms including nausea, vomiting, abdominal pain, diarrhea, and constipation.
There is specific gastrointestinal complications of renal replacement therapy these include idiopathic dialysis related ascites and dialysis related amyloidosis. There is another group of gastrointestinal complications related to peritoneal dialysis as infectious peritonitis and eosinophilic peritonitis, encapsulating peritoneal sclerosis.
Idiopathic ascites occurs in HD patients and may be due to suboptimal dialysis clearances. Diagnosis is by exclusion of other causes of ascites. Aspirated fluid usually has an elevated protein content. Management includes fluid and sodium intake restriction and ultrafiltration by dialysis. Small solute clearance must be optimized, and paracentesis may be required for symptom control. It may resolve after renal transplantation, and switching to PD can be tried. Amyloidosis due to deposition of β2-microglobulin in very rare patients on long-term dialysis can result in GI manifestations. These include GI hemorrhage, diarrhea, pseudo-obstruction, ischemia, and perforation.
A number of complications relating to PD may affect the abdomen, including infectious peritonitis, pain on dialysate infusion and drainage, and encapsulating peritoneal sclerosis. Hemoperitoneum in PD is typically related to the menstrual cycle, occurring during menstruation or ovulation, or may be self-limited, probably resulting from minor peritoneal membrane trauma from the PD catheter. Rarely, underlying pathologic causes are present, including encapsulating peritoneal sclerosis, malignant disease, pancreatitis, hepatobiliary disease, and hemorrhage from polycystic kidneys.
Encapsulating peritoneal sclerosis (EPS) represents the development of bowel obstructive symptoms due to encapsulation of the adhered intestinal tract forming a cocoon. The capsule continues from the visceral to parietal side of the peritoneum. The component of the capsule is fibrin that oozes from capillary blood vessels outgrowing in the deteriorated peritoneum and firmly covers the surface. Symptoms do not develop in the early stage because the capsule is thin, but bowel obstructive symptoms appear with thickening and shortening of the capsule with time that tighten the intestinal tract. Bowel obstructive symptoms progress slowly, rather than violently.
The incidence of gastrointestinal complications in renal transplantation is relatively high, ranging around 20%. These complications may be severe in about 10% of patients and may lead to graft loss and even patient death. Gastritis or duodenitis results from corticosteroid therapy, and mycophenolate mofetil commonly leads to diarrhea, abdominal pain, or vomiting. Infectious complications of the GI tract include oral and esophageal candidiasis, cytomegalovirus disease, and diarrhea from C. difficile. Post-transplantation lympho-proliferative disease may also involve the GI tract.