PBL: End Stage Renal Disease

Theme: Love my cheesecake but hate my injections

Keywords:

• 37 y/o woman visited nephrologist
• history of diabetes (since 15) & started on insulin injections (type 1)
• history of hypertension(2 years) & under control with Atenolol (B-blocker)
• Non compliant with her diet, insulin injections & doctor visits
• worried that might end up like mother with end stage renal disease
• fundoscopic exam: retinopathy
• urinalysis:
• glucose present
• protein, pus and haematuria not present
• blood sugar level increase
• HbA1C increased
• Microalbuminuria increased (early signs of renal disease)
• Serum creatinine & urea normal (kidney still functioning normally)
• Repeat test for microalbuminuria & 24 hour urine analysis
• Changed antihypertensive med to ACE inhibitor (cant give B-blocker for diabetics)

Hypothesis:

Early signs of renal disease

Learning issues:

1) Diabetes

• Complications

In type 1 diabetes, insulin is functionally absent because of the destruction of the beta cells of the pancreas. Type 1 DM occurs most commonly in juveniles but can occur in adults, especially in those in their late 30s and early 40s. Unlike people with type 2 DM, those with type 1 DM generally are not obese and may present initially with diabetic ketoacidosis (DKA).

Short term complications:

• hypoglycemia
• hyperglycemia
• ketoacidosis
• hyperosmolar syndrome (dehydration)

Long term complications:

• heart disease
• renal disease
• neuropathy
• retinopathy
• peripheral vascular disease
• diabetic dermadromes (skin rash)

2) End Stage Renal Disease

• Pathophysiology

All major organ systems are affected by renal failure. Prevalence of symptoms is a function of the glomerular filtration rate (GFR), which averages 120 mL/min in a healthy adult. As the GFR falls to less than approximately 20% of normal, symptoms of uremia may begin to occur. They almost are invariably present when the GFR decreases to less than 10% of normal. Measuring GFR requires a timed urine collection as well as measurement of serum creatinine. However, it can be accurately estimated from a patient’s age, weight, gender, and serum creatinine level. Online calculators are available to automate the calculation.²
Signs and symptoms of renal failure are due to overt metabolic derangements resulting from inability of failed kidneys to regulate electrolyte, fluid, and acid-base balance; they are also due to accumulation of toxic products of amino acid metabolism in the serum.

• Signs and symptoms include the following:

Systemic signs

Malaise, weakness, and fatigue are very common.

Gastrointestinal signs

GI disturbances include anorexia, nausea, vomiting, and hiccups. Peptic ulcer disease and symptomatic diverticular disease are common in patients with CRF. Malnutrition is common due to anorexia and digestive problems.

Neurologic signs

Peripheral neuropathy and restless legs syndrome are the most common neurologic complications of CRF. Seizures may occur due to uremia, and the prevalence of stroke is increased.

Hematologic signs

Anemia is inevitable in CRF because of loss of erythropoietin production. Abnormalities in white cell and platelet functions lead to increased susceptibility to infection and easy bleeding and bruising.

Dermatologic signs

Pruritus is a common dermatologic complication assumed to be secondary to accumulation of toxic pigments (urochromes) in the dermis.

Metabolic/endocrine signs

Volume overload occurs when salt and water intake exceeds losses and excretion. This causes congestive heart failure (CHF) and exacerbates hypertension. Hyperkalemia is the most common immediately life-threatening metabolic complication of renal failure and may develop suddenly when GFR is severely reduced. Anion gap acidosis results from decreased hydrogen ion excretion and may exacerbate hyperkalemia. Hypocalcemia is potentially life threatening and results from loss of vitamin D and increased parathyroid hormone levels. Hypermagnesemia also may occur. Hypothyroidism is common, and many of the symptoms overlap with the symptoms of uremia.
Cardiac signs

Volume overload may cause CHF and pulmonary edema. Hypertension contributes to cardiovascular disease. Dyslipidemia is a primary risk factor for cardiovascular disease and a common complication of ESRD. Uremia may also lead to pericardial effusion and, in rare cases, pericardial tamponade. Symptomatic pericarditis is much more common in the inadequately treated patient but occurs in patients receiving adequate dialysis. Cardiovascular mortality is 10-20 times higher in dialysis patients than in the normal population, and both CRF and ESRD are independent risk factors for heart disease.
Vascular signs

Vascular access complications are similar to those seen in any patient with a vascular surgical procedure (eg, bleeding, local or disseminated intravascular infections, vessel [graft] occlusion). The native peripheral vascular system is also affected with higher rates of amputation and revascularization procedures.
Dialysis catheters

A peritoneal dialysis catheter subjects patients to the risks of peritonitis and local infection. The catheter acts as a foreign body and provides a portal of entry for pathogens from the external environment.

Infection/immunologic

Uremia depresses the immune system, and ESRD patients are at increased risk of bacterial infection. Patients who have received renal transplants may experience recurrent renal failure due to rejection or other graft complications. In addition, chronic immunosuppression makes them prone to infection including opportunistic organisms.

• Causes

Once chronic renal failure (CRF) has occurred, treatment options and complications are largely independent of the cause.

• In terms of broad categories of disease, glomerulonephritis and interstitial nephritis are the most common causes of CRF in adults and children.
• Chronic upper urinary tract infection causes CRF in all age groups.
• CRF also is encountered in children because of congenital anomalies such as chronic hydronephrosis, which is caused by anatomic defects that obstruct urine flow or allow reflux from the bladder (vesicoureteral reflux).
• Kidneys may be congenitally hypoplastic.
• Hereditary nephropathies also exist.
• In adults, d
  iabetic and hypertensive nephropathies are the most common specific causes of CRF.
• Polycystic disease, renal vascular disease, and analgesic nephropathy also are common.
• In certain geographic areas, HIV-related renal disease is becoming common.
• Certain diseases such as some of the types of glomerulonephritis tend to recur in transplanted kidneys. In these cases, dialysis is the preferred treatment option.
• Consider renal transplant patients to be mildly to moderately immunosuppressed.
  • In the immediate posttransplant period or during a rejection episode, intensive immunosuppression puts patients at considerable risk of infection, including disseminated viral infections such as herpes zoster.
  • Degree of immunosuppression is less late in the posttransplant course when corticosteroids alone may be used.

3) Microalbuminuria

Microalbuminuria (the measurement of trace amounts of albumin protein in the urine) is an important prognostic marker for kidney disease in a variety of disease states such as diabetes mellitus and hypertension. Until recently, conventional qualitative tests (chemical strips or dipsticks) for albuminuria did not detect the small increases in urinary albumin excretion seen in early stages of nephropathy. Newer laboratory tests can now detect very low levels of the protein, leading to improved management for these patients.

• Cutoff point (reversible)

Excretion of 30–300 mg of albumin/24 h (or 20–200 µg/min or 30–300 µg/mg of creatinine on two of three urine collections)

Cutoff: 20 microgram/min

• Creatinine
• Urea
• Symptomatic
• Others
• Clinical significance/Causes
• an indicator of subclinical cardiovascular disease
• marker of vascular endothelial dysfunction
• an important prognostic marker for kidney disease
  • in diabetes mellitus
  • in hypertension
• increasing microalbuminuria during the first 48 hours after admission to an intensive care unit predicts elevated risk for acute respiratory failure , multiple organ failure , and overall mortality
• a risk factor for venous thromboembolism
• Macroalbuminuria

Large amounts of albumin. Also known as albuminuria. Above the cutoff level of 20microgram/min.

4) HbA1C

Glycated hemoglobin (hemoglobin A1c, HbA_1c, A1C, or Hb_1c; sometimes also HbA1c) is a form of hemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic pathway by hemoglobin’s normal exposure to high plasma levels of glucose. Glycation of hemoglobin has been associated with cardiovascular disease, nephropathy and retinopathy in diabetes mellitus. Monitoring the HbA_1c in type-1 diabetic patients may improve treatment.

• Measuring HbA1C

here are a number of techniques used to measure A1C.

Laboratories use :

• high-performance liquid chromatography (HPLC)
• Immunoassay

Point of care (eg doctors surgery) devices use :

• Immunoassay
• Boronate Affinity Chromatography

In the United States, POC A1C tests are certified by the National Glycohemoglobin Standardization Program (NGSP) to standardise them against the results of the 1993 Diabetes Control and Complications Trial (DCCT)

5) Tests/Diagnosis

• 24 hour urine analysis
• test for microalbuminuria

The level of albumin protein produced by microalbuminuria cannot be detected by urine dipstick methods. A microalbumin urine test determines the presence of the albumin in urine. In a properly functioning body, albumin is not normally present in urine because it is retained in the bloodstream by the kidneys.

Microalbuminuria is diagnosed either from a 24-hour urine collection (20 to 200 µg/min) or, more commonly, from elevated concentrations in a spot sample (30 to 300 mg/L). Both must be measured on at least two of three measurements over a two to three month period.^[1]. An albumin level above these values is called "macroalbuminuria", or sometimes just albuminuria.

To compensate for variations in urine concentration in spot-check samples, it is more typical in the United Kingdom to compare the amount of albumin in the sample against its concentration of creatinine. This is termed the albumin/creatinine ratio (ACR)^[2] and microalbuminuria is defined as ACR ≥3.5 mg/mmol (female) or ≥2.5 mg/mmol(male)

6) Management principles/treatment

• Renal transplant
• Dialysis

In medicine, dialysis (from Greek "dialusis", meaning dissolution, "dia", meaning through, and "lysis", meaning loosening) is primarily used to provide an artificial replacement for lost kidney function in people with renal failure. Dialysis may be used for those with an acute disturbance in kidney function (acute kidney injury, previously acute renal failure) or for those with progressive but chronically worsening kidney function–a state known as chronic kidney disease stage 5 (previously chronic renal failure or end-stage kidney disease). The latter form may develop over months or years, but in contrast to acute kidney injury is not usually reversible, and dialysis is regarded as a "holding measure" until a renal transplant can be performed, or sometimes as the only supportive measure in those for w
hom a transplant would be inappropriate.^[1]

The kidneys have important roles in maintaining health. When healthy, the kidneys maintain the body’s internal equilibrium of water and minerals (sodium, potassium, chloride, calcium, phosphorus, magnesium, sulfate). Those acidic metabolism end products that the body cannot get rid of via respiration are also excreted through the kidneys. The kidneys also function as a part of the endocrine system producing erythropoietin and 1,25-dihydroxycholecalciferol (calcitriol). Erythropoietin is involved in the production of red blood cells and calcitriol plays a role in bone formation.^[2] Dialysis is an imperfect treatment to replace kidney function because it does not correct the endocrine functions of the kidney. Dialysis treatments replace some of these functions through diffusion (waste removal) and ultrafiltration (fluid removal).

Principle

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.^[5] 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).^[5]

The two main types of dialysis, Hemodialysis (HD) and Peritoneal dialysis (PD), remove wastes and excess water from the blood in different ways.^[1] Hemodialysis removes wastes and water by circulating blood outside the body through an external filter, called a dialyzer, that contains a semipermeable membrane. The blood flows in one direction and the dialysate flows in the opposite. The counter-current flow of the blood and dialysate maximizes the concentration gradient of solutes between the blood and dialysate, which helps to remove more urea and creatinine from the blood. The concentrations of solutes (for example potassium, phosphorus, and urea) are undesirably high in the blood, but low or absent in the dialysis solution and constant replacement of the dialysate ensures that the concentration of undesired solutes is kept low on this side of the membrane. The dialysis solution has levels of minerals like potassium and calcium that are similar to their natural concentration in healthy blood. For another solute, bicarbonate, dialysis solution level is set at a slightly higher level than in normal blood, to encourage diffusion of bicarbonate into the blood, to act as a pH buffer to neutralize the metabolic acidosis that is often present in these patients. The levels of the components of dialysate are typically prescribed by a nephrologist according to the needs of the individual patient. In peritoneal dialysis, wastes and water are removed from the blood inside the body using the peritoneal membrane as a natural semipermeable membrane. Wastes and excess water move from the blood, across the peritoneal membrane, and into a special dialysis solution, called dialysate, in the abdominal cavity which has a composition similar to the fluid portion of blood.

Types of dialysis

There are two primary types of dialysis and another two types in addition, they are namely hemodialysis , peritoneal dialysis, and thirdly investigational type and finally intestinal dialysis.

[edit] Hemodialysis

Hemodialysis schematic

Main articles: Hemodialysis and Home hemodialysis

In hemodialysis, the patient’s blood is then pumped through the blood compartment of a dialyzer, exposing it to a partially permeable membrane. The dialyzer is composed of thousands of tiny synthetic hollow fibers. The fiber wall acts as the semipermeable membrane. Blood flows through the fibers, dialysis solution flows around the outside the fibers, and water and wastes move between these two solutions.^[6] The cleansed blood is then returned via the circuit back to the body. Ultrafiltration occurs by increasing the hydrostatic pressure across the dialyzer membrane. This usually is done by applying a negative pressure to the dialysate compartment of the dialyzer. This pressure gradient causes water and dissolved solutes to move from blood to dialysate, and allows the removal of several litres of excess fluid during a typical 3 to 5 hour treatment. In the US, hemodialysis treatments are typically given in a dialysis center three times per week (due in the US to Medicare reimbursement rules); however, as of 2007 over 2,500 people in the US are dialyzing at home more frequently for various treatment lengths.^[7] Studies have demonstrated the clinical benefits of dialyzing 5 to 7 times a week, for 6 to 8 hours. These frequent long treatments are often done at home, while sleeping but home dialysis is a flexible modality and schedules can be changed day to day, week to week. In general, studies have shown that both increased treatment length and frequency are clinically beneficial.^[8]

[edit] Peritoneal dialysis

Schematic diagram of peritoneal dialysis

Main article: Peritoneal dialysis

In peritoneal dialysis, a sterile solution containing glucose 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). ^[9] 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, and it can be done while travelling with a minimum of specialized equipment.

[edit] Hemofiltration

Main article: Hemofiltration

Hemofiltration is a similar treatment to hemodialysis, but it makes use of a different principle. The blood is pumped through a dialyzer or "hemofilter" as in dialysis, but no dialysate is used. A pressure gradient is applied; as a result, water moves across the very permeable membrane rapidly, "dragging" along with it many dissolved substances, importantly ones with large molecular weights, which are cleared less well by hemodialysis. Salts and water lost from the blood during this process are replaced with a "substitution fluid" that is infused into the extracorporeal circuit during the treatment. Hemodiafiltration is a term used to describe several methods of combining hemodialysis and hemofiltration in one process.

[edit] Intestinal dialysis

In intestinal dialysis, the diet is supplemented with soluble fibres such as acacia fibre, which is digested by bacteria in the colon. This bacterial growth increases the amount of nitrogen that is eliminated in fecal waste.[1] [2][3] An alternative approach utilizes the ingestion of 1 to 1.5 liters of non-absorbable solutions of polyethylene glycol or mannitol every fourth hour.

• Antihypertensive: Atenolol & ACE inhibitors

7) Evidence based Medicine

• Early intervention of microalbuminuria

Diabetics are checked for microalbumin.