1. Identification of potentially treatable causes of renal disease. There must be a concerted initial evaluation of the etiology of disease and for identification of potentially treatable aspects.
2. An intervention aimed at delaying disease progression. All appropriate means should be used to preserve renal function. This requires the presence of renal disease be appreciated at an early point, occasionally when the serum creatinine is still grossly normal.
3. Early identification and treatment of anemia to ensure that treatment is initiated to maintain the serum hemoglobin between 10-12 g/dl. The heart’s response to anemia is the development of left ventricular hypertrophy. This maladaptive response is an independent risk factor for mortality.
4. Adequate treatment of hypertension. This links closely with objective No. 2 above-intervention aimed at delaying disease progression. Renal disease often makes it difficult to control hypertension, so blood pressure control often develops into a major focus of therapy.
5. Early identification and treatment of renal osteodystrophy. Secondary hyperparathyroidism must be identified before severe renal disease develops, and then treated appropriately. Early treatment with vitamin D analogs may have an important salutary effect on bone pathology.
6. Maintaining good nutrition. Patients should receive comprehensive education and counseling regarding nutritional aspects of their disease. Usually this requires consultation with a dietitian with expertise in renal disease.
7. Identification and treatment of electrolyte and acid-base disturbances. A variety of metabolic derangements develop in the course of renal disease, requiring ongoing management.
8. Ensuring that the patient’s comorbid conditions are being intensively treated. This applies, as discussed above, for cardiac disease and diabetes, but also for any other important coexistent disease state.
9. Identification and intervention for psychosocial risk. Psychosocial factors greatly affect quality of life and may adversely impact medical outcomes. There must be a formal attempt to identify patients at increased psychosocial risk.
10. Appropriate disease education. A staged approach should be used to gradually help the patient understand kidney disease and its related problems. This is vitally important for reducing patient anxiety, improving compliance, and making the patient a partner in the care plan.
11. Early modality selection and vascular access placement. The patient with progressive renal disease needs to be directed on the need to choose an ESRD treatment modality well in advance of reaching ESRD. If renal transplantation is an appropriate option, then this option should be fully explained to the patient and early preparation initiated. If hemodialysis is to be the modality selection, then an arm should be protected, and an arteriovenous fistula should be placed 3—12 months prior to intended use.

Treatment Options

Dialysis and transplantation are life-prolonging therapies for many patients with renal insufficiency. Initially, patients with ESRD are managed with conservative therapy, but eventually, they require hemodialysis, peritoneal dialysis, and/or transplantation.

The correlation of uraemic symptoms with renal function varies from patient to patient depending on the cause of renal disease (earlier onset of symptoms in subjects with diabetes mellitus), muscle mass (large, muscular patients tolerate high levels of azotemia), diet, nutritional status, and coexisting conditions.

Dialysis and/or transplantation

Selection of patients to receive dialysis and/or transplantation is a matter of some debate. Because of the reversible nature of the acute renal failure, all patients with this diagnosis should be supported with dialysis, at least for some period of time, to allow the return of renal function.

The recipient should be free of life-threatening extrarenal complications such as cancer, severe coronary artery disease, and cerebrovascular disease. Provided that diffuse vascular involvement is not present, diabetes mellitus is not a contraindication. Oxalosis may recur in relatively short order in a transplanted kidney and is generally a contraindication for transplantation.

Criteria for treatment with hemodialysis or peritoneal dialysis are more liberal because dialysis has less morbidity than transplantation in older patients with the aforementioned medical complications.

Preparation for Therapy of End-stage Renal Disease

While conservative measures are being carried out in patients with chronic renal failure, it is important to prepare them with an intensive educational program, explaining the likelihood and timing of complete renal failure and the various forms of therapy available. The more knowledgeable patients are concerning hemodialysis, peritoneal dialysis, and transplantation, the easier and more appropriate.

Dialysis

Hemodialysis

Hemodialysis employs the process of diffusion across a semipermeable membrane to remove unwanted substances from the blood while adding desirable components. A constant flow of blood on one side of the membrane and a cleansing solution (dialysate).

Hemodialysis equipment consists of three components: the blood delivery system, the composition and delivery system of the dialysate, and the dialyzer itself. Blood is pumped to the dialyzer by a roller pump through lines with appropriate equipment to measure flow and pressures within the system; blood flow should be approximately 300 to 450 mL/min.

Peritoneal dialysis

Peritoneal dialysis, like hemodialysis, may be performed in various settings and with several techniques. In patients with acute renal failure, intermittent peritoneal dialysis(IPD) has largely been replaced by CAVHD (Continuous arteriovenous hemodialysis). Chronic peritoneal dialysis was attempted in the late 1940s but was impractical until the development of a permanent peritoneal catheter, the Tenckhoff catheter.

Transplantation

Transplantation of the human kidney is frequently the most effective treatment of advanced chronic renal failure. Worldwide, tens of thousands of such procedures have been performed. When azathioprine and prednisone were initially used as immunosuppressive drugs, the results with properly matched familial donors were superior to those with organs from cadaveric donors, namely, 75 to 90 percent compared with 50 to 60 percent graft survival rates at 1 year. During the 1970s and 1980s, the success rate at the 1-year mark for cadaveric transplants rose progressively.

Donor selection

Donors can be cadavers or volunteer living donors. The latter are usually family members selected to have at least partial compatibility for HLA antigens.

Tissue Typing and Clinical Immunogenetics

Matching for antigens of the HLA major histocompatibility gene complex is the ideal criterion for selection of donors for renal allografts.

Living Donors: When first-degree relatives are donors, graft survival rates at 1 year are slightly greater than those for cadaver grafts, with the exception of HLA-identical donors

Causes of renal failure

Collagen-related disorders

• Hypertrophy/hypoplasia
• Systemic lupus erythematosus
• Polyarteritis nodosa
• Progressive systemic sclerosis
• Metabolic disorders
• Diabetes mellitus
• Urate nephropathy
• Chronic urinary tract infections
• Oxalate nephropathy
• Amyloidosis

Congenital defects

• Polycystic kidney disease
• Renal tubular acidosis
• Alport’s syndrome
• Medullary cystic disease
• Obstructive nephropathy
• Ureteral or urethral strictures
• Calculi
• Neoplasms
• Retroperitoneal fibrosis or tumours
• Prostatic disease
• Congenital anomalies
• Glomerular diseases
• Glomerulonephritis
• Acute nephrotic syndrome
• Tubular damage
• Hereditary cellular membrane defects
• Chronic electrolyte imbalances (proximal and distal tubular acidosis, hypokalemia nephropathy, calcium nephropathy) disorders
• Infectious disorders
• Reflux chronic nephritis
• Analgesic nephropathy
• Idiopathic disorders

Vascular problems

• Sclerosis and narrowing of the afferent and efferent arterioles and glomerular capillaries
• Nephrosclerosis
• Renal artery sclerosis
• Hypertension

Symptoms of impending kidney disease are often deceptively mild in comparison to the potential severity of the disorder. In CRF, the parenchymal cellular function is slowly lost. All function of one kidney and two-thirds of the other may be gone before signs and symptoms appear.

Renal function is evaluated by the GFR, which indicates the amount of a substance cleared from the blood in one minute. When the GFR begins to fall and the BUN and creatinine levels rise, there is a tendency toward rapid progression to end-stage renal failure.

The clinical manifestations of CRF can be described as uraemia. The term uraemia describes a number of complex symptoms resulting from the accumulation of toxins in the blood because of a decline in renal function. In advanced uraemia, some functions of virtually every organ system in the body may become abnormal.

Clinical manifestation of uraemia

Cardiopulmonary system

• Hypertension
• Pericarditis
• Congestive heart failure
• Pulmonary edema
• Dysrhythmias

Neurologic system

• Fatigue
• Lethargy
• Muscular irritability
• Peripheral neuropathology
• Seizures
• Mental confusion
• Coma

Dermatologic system

• Pallor
• Hyperpigmentation
• Pruritis
• Ecchymosis
• Dry skin
• Uraemic frost

Metabolic system

• Protein intolerance
• Carbohydrate hyperglycemia
• Hyperlipidemia
• Gastrointestinal system
• Anorexia
• Nausea
• Vomiting
• Urinous breath
• Gastritis
• Gastrointestinal bleeding
• Diarrhea
• Peptic ulcers

Reproductive system

• Sexual dysfunction
• Menorrhagia
• Amenorrhea
• Infertility
• Decreased libido
• Decreased testosterone

Hematologic system

• Anaemia
• Hemolysis
• Bleeding tendencies
• Decreased resistance to infection

Skeletal system

• Pathologic fractures
• Bone inflammation
• Osteitis fibrosa
• Osteomalacia

Evaluation of CRF is based on the history and presenting signs and symptoms. Ultrasound, IVP, renal angiography, or scan and imaging tests are used to evaluate renal abnormalities. Renal biopsy can confirm a diagnosis. Blood tests may include a complete blood count, evaluation of blood gases, serum protein, BUN, creatinine, and uric acid levels.

The treatment for CRF has two stages. The first stage consists of conservative measures that include reducing symptoms, preventing complications, and controlling problems. Conservative measures include

• Determining and treating the cause of the renal failure; maintaining salt and water balance;
• Correcting any urinary tract obstruction;
• Detecting and treating infections early;
• Controlling hypertension;
• Consuming a low protein, high calorie diet;
• Preventing and treating renal bone disease;
• Modifying drug therapy with alterations in renal function; and
• Detecting and treating complications (eg, hyperkalemia, anemia, metabolic acidosis, hyperthyroidism.

These conservative measures help to delay the progressive deterioration of renal function. For example, hypertension must be treated, salt and water intake controlled, urine output maintained at as high a level as possible, and protein intake reduced to keep down the level of urea in the blood. The second stage of CRF begins when conservative measures are no longer effective. Then, the only treatments are either dialysis or transplantation.

Management

The clinical management of the patient with progressive renal failure may be divided into several components:

1. Early recognition of renal failure;
2. Monitoring the progression of renal failure;
3. Detection and correction of reversible causes of renal failure;
4. Institution of interventions to delay progression of renal failure;
5. Avoidance of additional renal injury;
6. Treatment of complications (ie, acid-base, mineral, and fluid-electrolyte abnormalities) of renal failure; and
7. Planning ahead for renal replacement therapy (dialysis or transplantation).

Causes of Acute Renal Failure

Traditionally, the causes of acute renal failure are classified as prerenal, intrarenal, or postrenal.

Prerenal Causes

Prerenal causes of acute renal failure are common, with intravascular volume depletion being the most common cause. Fever, vomiting, and diarrhoea can lead to decreased kidney perfusion. Dehydration from any cause, including diuretics, can precipitate acute renal failure.

Prerenal azotemia occurs in diseases that lead to a decrease in the effective arterial blood volume. These diseases include heart failure, liver failure, and nephrotic syndrome.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme (ACE) inhibitors are known to cause prerenal azotemia. NSAIDs affect the kidney by blocking cyclo-oxygenase, leading to an increase in thromboxane A2, which is a potent vasoconstrictor of the preglomerular arterioles. Because these afferent vessels supply blood to the kidney, vasoconstriction causes decreased glomerular perfusion.

ACE inhibitors block the production of angiotensin II, causing vasodilation of the postglomerular efferent arterioles. The vasodilation results in a decrease in the glomerular pressure, which may cause azotemia.

Large-vessel diseases, such as thrombosis, embolus, and dissection, also can reduce renal perfusion.

Intrarenal Causes

Intrarenal causes of acute renal failure are classified as tubular, glomerular, interstitial, and vascular.

Injury to the tubules most often is caused by ischemia or nephrotoxins. If prerenal azotemia and poor perfusion continue without treatment, tubular cells begin to die. This condition is termed “acute tubular necrosis.” Acute tubular necrosis is not a separate entity; rather, it is a marker of a more severe ischemic insult to the kidneys. Therefore, prerenal azotemia and tubular ischemia represent stages in the continuum of tubular injury.

Acute tubular necrosis has three phases: initiation, maintenance, and recovery. After the initial insult to the kidneys, the maintenance phase typically lasts one to two weeks. During the recovery phase, there may be marked diuresis and a slow return of kidney function. To date, no therapy has been shown to hasten recovery from acute tubular necrosis.

Efforts should be made to prevent the development of acute tubular necrosis in high-risk patients. Conditions that place patients at risk for this condition include untreated prerenal azotemia and the use of nephrotoxic drugs or exposure to other nephrotoxins

Postrenal causes

Postrenal causes of acute renal failure result in obstruction of the outflow tracts of the kidneys. Causes include prostatic hypertrophy, catheters, tumors, strictures, and crystals. The neurogenic bladder also can cause an obstruction.

Because postrenal causes are readily reversible, it is imperative to exclude them. Recovery of renal function is directly proportional to the duration of the obstruction. Renal ultrasonography can be used to assess patients for hydronephrosis because no contrast dye is used, renal function is not further compromised.

Excretory

• Maintains plasma osmology
• Maintains plasma pH
• Maintain the plasma concentration of electrolytes
• Excretes nitrogenous end products of protein metabolism

Nonexcretory

• Produces renin
• Produces erythropoietin
• Metabolizes vitamin D
• Degrades insulin
• Produces prostaglandin