Kidney diseases: pathophysiology, types, diagnosis and treatments


The kidneys are two bean shaped organs that are located in the flanks and serve mainly excretory functions. Drugs are eliminated through the kidneys by glomerular filtration and active tubular secretion. The kidneys becomes even more important as clinicians must always ascertain the state of renal function, especially when placing patients on drugs that are predominantly eliminated through them.
The functional unit of the kidney is the Nephron and the number of Nephrons in the normal individual ranges from approximately 300,000 to 1,000,000. New Nephrons are not added after birth and there is physiologic decline in their numbers, beginning at the age of 40years.

Types of Kidney or Renal disease

Renal disease may be:

  1. Acute Renal disease

  2. Chronic renal disease

Acute renal failure may be described as worsening of renal function over hours to days; while chronic renal failure is the loss of renal function over months to years.

Acute renal disease or failure

Although renal disease is a health concern of global proportion, the disease seems to be relatively more manageable in the developed societies. This may be due to presence of efficient and sophisticated diagnostic techniques as well as availability of various treatment options. Considering the developing nature of most African nations, however, renal disease, particularly end-stage renal failure remains mostly a fatal disease.

Definition or meaning of acute renal disease

Acute renal failure (ARF) is defined as the sudden, potentially reversible interruption or decline of kidney function resulting in the retention of nitrogenous waste products (e.g., Urea, Creatinine) and other substances in body fluids. Retention of these substances in the body is termed azotemia. in this condition, the body loses its ability to maintain fluid and electrolyte balance and to excrete nitrogenous wastes.

Classification and etiology

Renal function fails abruptly in a bewildering variety of clinical situations that lack common clinical pattern. This renders it difficult to discuss causation generally. Nevertheless, it is a diagnostically useful to classify acute renal failure into 3 categories

  1. Pre-renal azotemia

  2. Post-renal azotemia

  3. Intrinsic renal azotemia

Pre-renal Azotemia

Pre-renal azotemia is the most common cause of acute renal failure and occurs as a result of renal hypoperfusion. Decreased renal blood flow can occur as a result of

  1. Decrease in intravascular volume
  2. A low cardiac output and a change in
  3. Vascular resistance

Decrease in intravascular volume may be caused by haemorrhage, gastrointestinal losses, excessive diuresis, burns, trauma and dehydration. While low cardiac output maybe precipitated by cardiogenic shock, pulmonary embolus, peripheral tampnade and CHF among others, changes in vascular resistance can occur systematically with sepsis. Anaphylaxis, anaesthasia, and other load-reducing drugs. Epinephrine, norepinephrine, high-dose dopamine and cyclosporine can all cause renal vasoconstriction with a resultant decrease in renal perfusion. If hypoperfusion persists, ischaemia can result, causing intrinsic renal failure, but if immediately reversed with restoration of renal blood flow; pre-renal azotemia does not lead to intrinsic renal failure.
Post-renal azotemia is the least common cause of acute renal failure, and occurs when there is obstruction of urinary flow from both kidneys. The obstruction  in the urinary tract may be as a result of urethral obstruction, bladder dysfunction or obstruction and obstruction of both urethras or renal pelvis.
Other cause of obstruction include benign prostatic hyperplasia (especially in old men), bladder, cervical and prostate cancers,  as well as neurogenic bladderless common cause, include blood clots. Bilateral ureter stones structures and bilateral papillary necrosis.  In patients with a single functioning kidney, obstruction of a solitary ureter can cause post-renal azotemia.

Etiology and classification of acute renal failure


  • Pre-renal azotemia caused by poor renal perfusion
  • Post-renal azotemia caused by obstruction of urinary bladder
  • Intrinsic real disease
  • Acute tubular necrosis caused by ischaemia presence of nephrotoxins
  • Acute glomerulonephritis caused by post streptococcal, collagen vascular disease
  • Acute  interstitial nephritis caused by allergic reaction drug runs idiopathic

Intrinsic renal failure accounts for about half of all cause of acute renal failure with acute tubular necrosis (ATN) accounting for about 85% of all case. The major causes of ATN are;

  1. Ischemia
  2. Toxin exposure

However, it is important to know that low perfusion preceded by a state of renal azotemia, often leads to ischemia and tubular damage. Acute tubular necrosis (ATN) also results from nephrotoxin, it may be exogenous or endogenous in nature. Exogenous nephrotoxin, primarily drugs, cause tubular damage more commonly than endogenous toxins.
Some of the common nephrotoxin drugs include

  • Gentamicin, amphotericin B. vancomycin, acyclovir, cephalosporins, NSAIDS and ACE inhibitors.
  • Endogenous nephroprotoxins include haem-containing products, uric acid, and paraproteins. Acute interstitial nephritis (AIN) accounts for 10-15% of all causes of intrinsic renal failures. Drugs account for over 70% of all cases of AIN, the most common ones being penicillin’s and cephalosporins, sulphonamides and sulphonamide-containing diurectics NSAID, rifampicin, phenytoin and allopurinol. Other causes of AIN are either injections disease or immunologic disorders. Acute glomerulonephritis is a relatively uncommon cause of acute renal failure and accounts for about 5% of all cases of intrinsic renal disease.

Chronic Kidney disease

Chronic kidney disease is the progressive irreversible deterioration, of renal function and usually result from long standing disease CKD sometimes derives from ARF that does not respond to treatment.

Classification and pathophysiology

  1. CKD  is defined as kidney damage of Glomerular filtration rate (GFR rate) (GFR) <  60ml/min/1.73m2 for   > 3 months kidney damage  is defined as pathological abnormalities or markers of damages, including abnormalities in blood or urine tests or imaging studies.

Chronic kidney disease has recently been reclassified as stage 1-v to denote the severity of renal impairment. Generally, ckd,  if left untreated progress at a predictable steady  rate from stage 1 through stage v.
Stage 1 is defined as kidney damage with a normal or real GFR. The corresponding GFR in stage 1 chronic kidney disease is usually > 90ml/min/1.73m2
Stage 2 is defined as kidney damage or a mildly decreased GFR. (60-89ml/min/1.73m2)
Stage 3 signifies moderate reductions in GFR (30-59ml/min/1.73m2)
Stage 4 connotes a GFR of 15-29ml/min/1.73m2
Stage 5 is kidney failure or a GFR of < 15ml/min/1.73m2

  1. As chronic kidney disease (CKD) progresses, nephron destruction worsens, leading to deterioration in the kidney’s filteration reabsorption and endocrine functions.  Over 50% of all cases of chronic renal failure are due to to diabetes mellitus and hypertension. And while glomerulonephritis, cystic diseases, and certain other urologic diseases account for another 20-25% about 0.2% of all cases of chronic renal failure are idiopathic

Causes of chronic renal failure

The major causes of chronic renal failure are listed below.


Primary glomerular disease

  1. Ig A nephropathy
  2. Membranous nephropathy

Secondary glomerular disease

  1. Diabetic nephropathy
  2. Amyloidosis
  3. Collagen-vascular disease
  4. Sickle cell nephropathy
  5. HIV-associated nephropathy

Tublointerstitial nephritic

  1. Drug hypersensitivity
  2. Analgesic  nephropathy
  3. Chronic pyelonephritis
  4. Idiopathic 

Heredity diseases

Obstructive nephropathic

  1. Prostatic disease
  2. Congenital disorders
  3. Vascular diseases

 Hypertensive nephrosclerosis

  1.  Renal artery stenosis.

Acute Glomerulonephritis (AGN), Postinfection Glomerulanephritis (PIGN)
A disease characterized pathologically by diffused inflammatory changes in the glomerula and clinically by the abrupt onset of haematuria with RBC cast and mild proteinuria and in many cases hypertension and azotemia.
The prototypic glomerular disease of acute onset is psotstreptococcal glomerulonephritis(PSGN). In this immune complex(IC) disease, Group AB hemotreptococcal antigens (nephritis strains 1, 4, 12, 29) provoke an antibody response and the resulting antibody complexes whether formed in situation circulating are deposited in the glomerular capillary walls.

Acute nephrotic syndrome 

A predictable complies that follows a severe prolonged increase in glomerula permeability for protein. The main features is proteinuria (>20m/m2/day or a random urinary ptotein creatinine ratio > 2),but hypoalbuminemia ()<3gm/dl, generalized edema, and lipemia also are frequently present to complete the syndrome complex. 

  1. Acute Bacterial Pyelonephritis (Acute Inflective Tubulointerstitial Nephritis) 

An acute, patch often bilateral, pyogenic infection of the kidney, clinically, infections of the renal pelvis and parendyma cannot be distinguished from each other and both sides are usually affected. Acute infective tubilo interstitial nephritis is a more descriptive terms.

  1. A disease characterized pathologically by diffuse inflammatory changes in the glomeruli and clinically by the abrupt onset of haematuria with RBC casts, Proteinuria and in many cases, HT, edema and azotemic.

Pharmacotherapy of renal disease

Pharmacotherapy is the treatment of diseases with medicines (drugs). This often times involves non-drug treatment, i.e., lifestyle  modifications. The therapeutic approach selected in the treatment of nephropathics is dependent on the  severity of the infection; the patient’s  history, existing pathologies, whether complicated or uncomplicated, extremes of age and the predisposing factors. The presence or absence of predisposing factors which can  influence the course of outcome of the current or possible future infections or occurrence should be considered.
In renal impairment, the use of drugs can give rise to problems for several reasons,

  • Failure to excrete a drug or its metabolites may produce toxicity
  • Sensitivity to some drugs is increased even if elimination is unimpaired
  • Many side effect are tolerated poorly by patients with renal failure
  • Some drugs ceases to be effective when renal function is reduced e.g. thiazide and related diuretics

Many of these problems can be avoided by reducing the dose by using alternative drugs

Principles of dose adjustment in renal impairment 

For prescribing purposes, renal impairment can be arbitrarily divided into three grades;
Grade (approximately)

  • 20-50ml/min (serum)
  • 150-300umol/litre (creatinine)


  • 10-20ml/min (serum)
  • 300-700umol/litre (creatinine)


  • <10ml/min (Serum)
  • >700umol/litre (Creatinine)

Creatinine is a normal plasma constituent and is derived from the creatinine normally found in muscle tissues
Creatinine clearance is between 91mL-130mL/min. creatinine is toxic and is excreted primarily by the kidney. Under normal circumstances, its level in the blood is stable. Because creatinine is freely filtered at the glomerulus and none is reabsorbed, the amount present in the urine reflects the glomerular filtration rate (GFR)
Creatinine is a crystalizable nitrogenous compound synthesized in the body. 
Creatinine- a waste product formed from creatinine and phosphocreatine
Other principles of dose adjustment in renal impairment include;

  • The level of renal function below which the dose of a drug must be reduced depends on whether the drug is eliminated entirely by the renal excretion or is partly metabolized, and how toxic it is
  • Drug with only minor or not dose-related side-effects modification of the dose regimen necessary, a simple scheme for dose reduction is sufficient.
  • For more toxic drugs with a small safety margin dose regimens based on glomerular filtration rate should be used.
  • Adjustment can also be done by clinical response and plasma concentration.

Acute Renal Failure

Acute renal failure occurs in approximately 0.37% – 5% of all hospitalized patients. It is most often caused by a combination of event including sepsis, hypotension and exposure to nephrotic drugs and therapeutic agents.

Definition of acute renal failure

Acute renal failure(ARF)  is the  sudden, potentially reversible interruption of kidney function, resulting in retention of nitrogenous waste products in body fluids
Typical findings in ARF include the following;

  • Increased BUN
  • Increased serum creatinine concentration
  • Possible increase in hemoglobin and hematocrit values due to dehydration
  • Abnormal serum electrolyte values
  • Serum K level above 5mEq/L
  • Serum phosphate level above 2.6mEq/L
  • Serum Ca level below 4mEq/L(hypocalcemia)
  • Serum Na level above 135mEq/L(hyponatremia)
  • Abnormal arterial blood gas values (pH below 7.35, HCO below 22) reflecting metabolic acidosis.

Treatment objectives/Goals

  • Correct reversible causes of ARF,  preventing or minimizing further renal damage or complications
  • Correct and maintain proper fluid and electrolyte balance
  • Match fluid, electrolyte and nitrogen intakes to urine output
  • Treat body chemistry alterations, especially hyperkalemia and metabolic acidosis, when present. Treatment may include renal dialysis
  • Improve urine output
  • Treatment systematic manifestations of ARF


Conservative management alone may suffice  in uncomplicated ARF

Fluid management

  1. Fluid intake should match fluid losses
  2. Volume overload should be avoided to minimize the risk of hypertension and CHF
  3. The patients should be weighed daily to determine fluid volume status

Dietary measures

Because catabolism accompanies renal failure, the patient should receive a high-calorie, low-protein diet. Such a diet helps to:

  • Reduce renal workload by decreasing production of end products of protein catabolism that the kidneys cannot excrete
  • Prevent ketoacidosis
  • Alleviate manifestations of uremia

If edema or hypertension is present, sodium intake should be restricted.
Potassium intake must be limited in most patients.
Fruits, vegetables and salt substitutes containing potassium should be limited or avoided.

Management of body chemistry alterations

Treatment of hyperkalemia

  • Dialysis may be used to treat acute, life threatening hyperkalemia.

Calcium chloride or calcium gluconate

Mode of action and therapeutic effects.

Calcium chloride  or calcium gluconate replaces and maintains body potassium, counteracting the cardiac effects of acute hyperkalemia.

Administration and dosage

When used to reverse hyperkalemia-induced cardiotoxicity, calcium chloride is given intravenously as 5-10ml of 10% solution administered over 2min.
Doses of up to 20ml of a 10% solution are safe when given slowly.
Another 10-20ml of 10% solution placed in a larger fluid volume and administered slowly may follow the initial dose.
Calcium gluconate  is administered as 10ml of a 10% solution (1g) over 2-5mins. This may be repeated a second time

Precautions and monitoring

  1. Intravenous Ca is contraindicated in patients with ventricular filbration or renal calculi
  2. The infusion rate should not exceed 0.5ml/min. patients should remain recumbent for about 15mins after infusion
  3. The ECG should be monitored during calcium gluconate therapy
  4. Calcium gluconate should not be mixed with solutions containing sodium bicarbonate because this can lead to precipitation

Adverse effects

These include hypotension, tingling sensations and renal calculus formation.

Significant interactions

Calcium may cause increased digitalis toxicity when administered concurrently with digitalis preparation.

Sodium bicarbonate

This may be given as an emergency measure for severe hyperkalemia or metabolic acidosis

Mode of action and therapeutic effect

  • IV sodium bicarbonate restores bicarbonate that the renal tubules cannot reabsorb from the glomerular filtrate and increases arterial pH.
  • This results in a shift of potassium into cells and reduces serum potassium concentration.

Onset of action is 15-30mins

Administration of dosage

  • Sodium bicarbonate is administered intravenously
  • The dosage is calculated as follows: [50% of body wt(kg)] x [desired arterial bicarbonate (HCO-3)-actual HCO-3].
  • One ampule (50mEq) may be given intravenously over 5mins

Precautions and monitoring effects

  1. To avoid sodium and fluid overload, sodium bicarbonate must be given cautiously. Half of the patient’s bicarbonate deficit is replaced over the first 12 hours of therapy
  2. Sodium bicarbonate may precipitate calcium salts in IV solution and should not be mixed in the same infusion fluid
  3. Arterial blood gas values and serum electrolyte levels should be monitored closely during sodium bicarbonate therapy.

Regular insulin with dextrose

Mechanism of action and therapeutic effect

The insulin causes an intracellular shift of potassium. The combination of insulin with dextrose deposits potassium with glycogen in the liver, reducing the serum potassium

Onset of action 15-30mins

Administration and dosage

Regular insulin (10 units in 500ml of 10% dextrose) is administered intravenously over 60mins

Precautions and monitoring effects

  1. The serum glucose level should be monitored during therapy.
  2. The patient should be assessed for signs and symptoms of fluid overload.

 Sodium polystyrene sulfonate (SPS) (kayexalate) 

Mechanism of action

SPS is a potassium-removing resin that exchanges sodium ion for potassium in the intestine. (1g of SPS exchanges 0.5ml-1mEq/L of potassium). The SPS is distributed throughout the intestines and excreted in the faeces.

Therapeutic effect

  1. Administered as an adjunctive treatment for hyperkalemia, SPS reduces potassium levels in the serum and other body fluids.
  2. Onset of action of orally administered SPS is 2 hours; effects are seen in 1 hour when SPS is administered as a retention enema.

Administration and dosage

  1. SPS is usually administered orally, although it may be given through a nasogastric tube. The oral dose is 15-30g in suspension of 70% sorbitol, administered every 4-6 hours until the desired  therapeutic effect is achieved.
  2. When oral or nasogastric administration is not possible due to nausea, vomiting, or paralytic ileus, SPS may be given by retention enema. The rectal dose is 30-50g in 100ml sorbitol, as a warm emulsion, administered deep into the sigmoid colon every 6 hours. Administration may be done with a rubber tube that is taped in place or via Foley catheter with balloon inflated distal to anal sphincter.

Precautions and monitoring effects

  1. The patient’s serum electrolyte levels should be monitored closely during SPS therapy. sodium chloride, bicarbonate and pH should  be monitored in addition to potassium.
  2. SPS therapy usually continues until the serum potassium level drops to between 4 and 5mEq/L
  3. The patient should be assessed regularly for signs of potassium depletion including irritability, confusion, cardiac arrhythmias, ECG changes and muscle weakness
  4. SPS exchanges sodium for potassium, so sodium overload may occur during therapy. patients with hypertension of CHF should be closely monitored.
  5. For oral administration, SPS should be mixed only with water or sorbitol, orange juice, which as a high potassium content, should not be used because it decreases the effectiveness of the SPS. For rectal administration, SPS should be mixed only with water or sorbitol, never with mineral oil.

Adverse effects

Adverse effects of SPS include constipation, fecal impaction, with  rectal administration, nausea, vomiting and diarrhea.

  • SPS should not be used as a sole agent in the treatment of severe hyperkalemia; other agents or therapies should be used in conjunction with this agent.

Significant interactions

Magnesium hydroxide and other nonabsorbablecation-donating laxatives and antacids may decrease the effectiveness of potassium exchange by SPS and may cause systematic alkalosis

Treatment of metabolic acidosis

Sodium bicarbonate may be given if arterial pH is below 7.35

Treatment of hyperphosphotemia

  1. IV calcium is the first-line therapy for severe life threatening hyperphosphotemia.

Calcium reduces the serum phosphorus concentration by chelation.

  1. Oral calcium salt bind dietary phosphorous in the GI tract.
  2. Sevelamer is a non-ionic polymer that binds dietary phosphorous in the GI tract.
  3. Dialysis may be used to treat acute, life-threatening hypophosphatemia accompanied by acute hypocalcemia. It is also performed when the volume overload is present.
  4. Aluminium hydroxide
  1. MOA and therapeutic Effect: Aluminum binds excess phosphate in the intestine, thereby reducing phosphate concentration
  2. Onset of action is 6 to 12 hours.
  3. Administration and dosage: Aluminum hydroxide is administered orally as a tablet or suspension. For treatment of hypophosphatemia, 0.5-2 or 15-30ml of suspension is administered 3 or 4 times daily with meals. 
  4. Precautions and monitoring effects
  • Aluminum hydroxide may cause constipation and anorexia
  • Serum phosphate levels should be monitored because aluminum hydroxide can cause phosphate depletion.
  • Aluminum hydroxide can cause calcium resorption and bone demineralization
  1. Treatment of hypocalcemia: Immediate treatment is necessary  if the patient has severe hypocalcemia, as evidenced by tetany.
  1. Calcium gluconate
  1. MOA and Therapeutic Effect: This drug replaces and maintains body calcium, raising the serum calcium level immediately
  2. Administration and dosage: When used to reverse hypocalcemia, caliumgluconate is administered intravenously in a dosage of 1-2g over a period of 10mins, followed by a slow infusion(over 6-8hours)of an additional 1g.
  1. Oral calcium source; Calcium carbonate, chloride, gluconate or lactate may be given by mouth when oral intake is permitted or if the patient has relatively mild hypocalcemia.  The usual adult dosage is 4-6g/day given in 3 or 4 divided doses.
  1. Treatment of hyponatremia
  1. Moderate or asymptomatic hyponatremia may require only fluid restriction
  2. Sodium chloride may be given for severe sympotamic hyponatremia (i.e a serum sodium level below 120 mEq/L)
  1. MOA and Therapeutic effect: Sodium chloride replaces and maintains sodium and chloride concentration, thereby increasing extracellular tonicity.
  2. Administration and dosage
  • A 3% or 5% sodium chloride solution may be administered by slow IV infusion
  • Typically, 400ml or less is administered
  1. Precautions and monitoring effect.
  • Hypertonic sodium chloride must be administered very slowly to avoid circulatory overload, pulmonary edema or central pontine demyelination
  • Serum electrolyte levels must be monitored frequently during therapy
  • Excessive infusion may cause hypernatremia and other serious electrolyte abnormalities may worsen exiating acidosis.  Infusion rates should not exceed 0.5mEq/kg/hr
  1. Management of systemic manifestations
  1. Treatment of fluid overload and edema: As water  and sodium accumulate in extracellular fluid during ARF, fluid overload and edema may occur. Diurectics and dopamine may be given to reduce fluid volume excess and edema. Treatment should be initiated as soon as possible after oliguria begins. Mannitol or a loop diuretics may be used; thiazide diurtetics are avoided in renal failure because they are ineffective when creatinine clearance is less than 25ml per minute and they may worsen the patient’s clinical status.

Step 1: Loop(high ceiling)  diuretics

  1. MOA and Therapeutic effect: Loop diuretics inhibits sodium  and chloride reabsorption at the loop of Henle, promoting water excretion.
  2. Onset of action for an oral dose is 1 hour; several minutes for IV dose. Duration of action of an oral dose is 6-8hours; 2-3 hours for an IV dose.
  3. Administration an dosage
  • Furosemide: the most commonly used diuretics is administered intravenously in patient with ARF to hasten the therapeutic effect. The dose is titrated to the patient’s need.
  • Bumatenide, may be given to patients who are unresponsive or allergic to furosemide. The usual dosage, administered intravenously or intramuscularly in the treatment of ARF.
  • Ethacrynic acid is less commonly used to treat ARF because ototoxicity(sometimes irreversible)  is associated  with its use
  • Torsemide may also be given to patients unresponsive to or allergic to furosemide. The usual dose is 20mg administered intravenously.
  1. Precautions and Monitoring effects
  • Loop diuretics must be used cautiously because they may cause over diuresis leading to orthostatic hypotension, fluid and electrolyte abnormalities, including volume depletion and dehydration, hypocalcemia, hypokalemia, hypchloremia, hyponatremia, hypomagnesemia and transient ototoxicity especially with rapid IV injection.
  • Serum electrolyte levels should be monitored frequently and the patient assessed regularly for signs and symptoms of electrolyte abnormalities.
  • Blood pressure and pulse rate  should assessed during diuretic therapy
  • GI reactions include abdominal pain and discomfort, diarrhea (with furosemide and ethacrynic acid) and nausea (with bumetanide)
  1. Significant interactions
  • Aminoglycosides antibiotics may potentiate ototoxicity when administered with any loop diuretic.
  • NSAIDS may hamper the diuretic  response to furosemide and bumetanide; probenecid may hamper the diuretic response  to bumetanide
  • Ethacrynic acid may potentiate the anticoagulant effects of warfarin.

Chronic Kidney Diseases


  • Chronic kidney disease is the progressive, irreversible deterioration of renal function
  • Usually resulting from long-standing disease, CKD sometimes derives from ARF that does not respond to treatment.

Classification and pathophsiology

  • CKD is defined as kidney damage or GFR < 60ml/min/1.73m2 for > 3months.kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies.
  • CKD has recently been reclassified as stages I-V to donate the severity of renal impairment. Generally, CKD if left untreated, progresses at a predictable steady rate from stage 1 through stage V

Classification and pathophsiology

  • Stage 1 is defined as kidney damage with a normal or increased GFR. The corresponding GFR in stage 1 CKD is usually > 90ml/miin/1.73m2.
  • Stage 2 is defined as kidney damage or a mildly decreased GFR (60-89ml/min/1.73m2)
  • Stage 3 siggnifues moderate reductions in GFR (30-59ml/min/1.73m2)

Classification and Pathophsiology

  • Stage 4 connotes a GFR of 15-29ml/min/1.73m2
  • Stage 5 is kidney failure or a GFR of < 15ml/min/1.73m2

As CKD progresses, nephron destruction worsens, leading to deterioration in the kidney filtration, reabsorption and endocrine  functions.

Etiology of CKD

  • Diabetic nephropathy
  • Hypertension
  • Glomerulonephritis
  • Polcystic kidney diseases
  • Long-standing vascular diseases (renal artery stenosis)
  • Long-standing obstructive uropathy (renal calculi)
  • Exposure to nephrotoxic agents

Clinical evaluation  

Physical findings

Signs and symptoms, which vary widely, do not appear until renal insufficiency progresses to renal failure

Metabolic Abnormalities

  • Include loss of the ability to maintain sodium, potassium and water homeostatis, leading to hyponatremia and hypernatremia, based on relative sodium or water in take.
  • Hyperkalemia is uncommon until end –stage disease.  fluid overload, edema and CHF may become a problem unless fluid intake is closely managed.
  • As renal failure progresses, the inability to excrete acid and maintain buffer capacity leads to metabolic acidosis. Calcium and phosphate metabolism is altered due to hyperparathyroidism

Neurological manifestations

  • Include short attention span, loss of memory and listlessness. As CKD progresses, these advance to confusion, stupor, seizures and coma.
  • Neuromuscular findings include peripheral neuropathy, pain, itching and a burning sensation, particularly in the feet and legs
  • Patients may appear intoxicated.  If dialysis is not started after

Clinical evaluation 

 Diagnostic test result that are related to clinical evaluation are as follows:

  1.  Creatinine  clearance may range from 0-9ml/min, reflecting  renal impairment
  2. Blood test typically shows.
  • Elevated BUN and serum creatinine concentration
  • Reduced serum calcium  level
  • Reduced arterial pH and bicarbonate concentration
  • Increased serum potassium and phosphate levels
  • Possible reduction in the serum sodium level
  • Normochromic, normocytic anemia (hematocrit 20%-30%)
  1. Urinalysis may reveal glycosuria, proteinuria, erythrocytes, leukocytes and casts. Specific gravity is fixed at 1.010
  2. Radiographic findings. Kidney, ureter, and bladder radiography,  IV pyelography, renal scan, rrenal arteriography, and nephrotomagraphy may be performed. Typically, these tests reveal small kidneys (less than 8cm in length)

Treatment objectives and goals

  • Improve patient comfort
  • Treat systemic manifestations of CKD
  • Correct body chemistry abnormalities


 Treatment of edema
ACE inhibitors and diuretics may be given to  manage edema and CHF and to increase urine ouput

ACE inhibitors

Captopril, enalapril, lisinopril, fosinopril- are widely used to delay progression of CKD because they help preserve renal function and typically cause fewer adverse effects than other antihypertensive agents. They also decrease proteinuria and nephrotic syndrome


An osmotic diuretic, a loop diuretic, or a thiazide-like diuretic may be given

  • Osmotic and loop diuretics
  • Thiazide-like diuretics.


Metolazone is the most commonly used thiazide-like diuretic in CKD.

Mode of action and therapeutic effect

Metolazone reduces the body’s fluid and sodium volume by decreasing sodium reabsorption in the distal convoluted tubule, thereby increasing urinary excretion of fluid and sodium.

Administration and dosage

  • Metolazone is given orally at 5-29mg/day; the dose is titrated to the patient’s needs.
  • Due to its long half-life metolazone may be given every other day.
  • Furosemide and metolazone act synergistically.
  • Combination  use is common and metolazone should be administered 30minutes before furosemide to achieve the optimal diuretic effect.

Precautions and monitoring effects

  • Metolazone should not be given to patients with hypersentivity to sulfonamide derivative, including thiazides.
  • To avoid nocturia, the daily dose should be given in the morning
  • Metolazone may cause hematological reaction, such as agraunulcytosis, aplastic anemia, and thrombocytopenia
  • Fluid volume depletion, hypokalemia, hyperuricemia, hyperglycemia and impaired glucose tolerance may occur during metolazone therapy
  • Metolazone may cause hypersentivity reactions including vasculitis and pneumonitis

Significant interactions

  • Diazoxide may potentiate the antihypertensive, hyperglycemic and hyperuricemic effects of metolazone
  • Colestipol and cholestyramine decrease the absorption of metolazone

Hypertension in CKD

Antihypertensive agents may be needed if blood pressure becomes dangerously high as a result of edema and the high renin levels that occur in CKD. Antihypertensiv therapy should be initiated in the lowest effective dose and titrated according to the patient’s need

  1. ACE inhibitors-captopril, enalapril, lisinopril, fosinopril
  2. Dihyropyridine calcium-channels blockers, including amlodipine and felodipine, have similar effects and may be used instead of ACE inhibitors
  3. B-adrenergic blockers, including propranolol and atenolol, reduce blood pressure through various mechanisms.
  4. Other antihypertensive agents are sometimes used in the treatment of CKD including a-adrenergic drugs, clonidine and vasodilators, such as hydralazine


 Treatment of hyperphosphatemia in CKD

This involves administration of phosphate binder, such as aluminum hydroxide or calcium carbonate

Treatment of hypokalemia in CKD 

  1. Oral calcium salts
  2. Vitamin D

Mode of action and therapeutic effect.

Vitamin D promotes intestinal calcium and phosphate absorption and utilization and thus, increases the serum calcium concentration

Choice of agent.

For  the treatment of hypokalemia in CKD and other renal disorders calcitrol (vit D3, the active from vitamin D) is the preferred vit D supplement because of its greater efficacy and relatively short duration of action.

Administration and dosage

Calcitrol is given orally or via IV; the dosage is titrated to the patient’s needs (0.5-1mg/day may be effective)

Precautions and monitoring effects

  1. Vitamin D administration may be dangerous in patients with renal failure and must be used with extreme caution.
  2. Vitamin D toxicity may cause a wide range of signs and symptoms, including headache, dizziness, ataxia, convulsion, psychosis, soft-tissue calcification conjuctivities, photophobia, tinnintus, nausea, diarrhea, pruritus and muscle and bone pain
  3. Vitamin D has a narrow therapeutic index necessitating frequent measurement of BUN and serum urine calcium and potassium levels.

 Treatment of other systematic manifestations of CKD


Treatment of anamia incudes administration of

  • iron
  • foliate supplement and
  • erythropoietin
  • Severe anemia may warrant transfusion with packed RBC


  • Erythropoietin stimulates the production of red cell progenitors and the production of hemoglobin.
  • It also accelerates the release of reticulocytes from the bone marrow.


  1. An initial dose of enthropoietin is 50-100U/kg intravenously or subcutaneously three times a week. The dose may be adjusted upward to elicit the desired response
  2. Erythropoietin works best in patients with a hematocrit below 30 %. During the initial treatment, the hematocrit increases 1%-3.5% in 2 weeks period. The target hematocrit is 33%-35%.  Maintenance doses are titrated based on  hematocrit after this level is reached.
  3. Erythropoietin therapy should be temporarily stopped if hematocrit exceeds 36%.

Adverse effects

Side effects include hypertension up to 25% of patients. Headache and malaise have been reported

  1. The effect of erythropoietin are dependent on ready supply of iron for hemoglobin synthesis. Patients who do not respond should have iron stores checked. This includes serum iron, total iron-binding capacity, transferrin saturation and serum ferritin. Iron supplementation should be increased as indicated

 Treatment of GI  disturbances

  • Antiemetics help control nausea and vomiting
  • Docusate sodium or methylcellulose may be used to prevent constipation.
  • Enemas may be given to remove blood from the GI tract.

Treatment of skin problems

An antipruritic agent, such as diphenhydramine, may be used to alleviate itching

Management of body chemistry abnormalities


When CKD progresses to end-stage renal disease and no longer responds to conservative measures, long-term dialysis or renal transplantation is necessary to prolong life.

  1.  Hemodialysis is the preferred dialysis method for patients with a reduced peritoneal membrane, hypercatabolism, or acute hyprkalemia
  • This technique involves shunting of the patient’s blood through dialysis membrane containing unit of diffusion, osmosis, and ultrafiltration. The blood is returned to the patient’s circulation.
  • Vascular access may be obtained via an arteriovenous fistula or an external shunt.
  • The procedures takes only 3-8hours; most patients need three treatments a week.
  • With proper training, patients can perform hemodialysis at home.
  • The patient receives heparin during hemodialysis to prevent clotting
  • Various complications may arise, including clotting of hemofilter, hemorrhage, hepatitis, anemia, septicemia, cardiovascular problems, air embolism, rapid shifts in fluid and electrolyte balance, itching, nausea, vomiting, headache, seizures and aluminum osteodystrophy.
  • Peritoneal dialysis is the preferred dialysis method for patients with bleeding disorders and cardiovascular disease
  • The peritoneum is used as a semipermeable membrane. A plastic catheter inserted into peritoneum provided access for the dialysate, which draws fluids, wastes, and electrolytes across the peritoneal membrane by osmosis and diffusion
  • Peritoneal dialysis can be carried  out in three different modes
  • Intermittent peritoneal dialysis is an automatic cycling mode lasting 8-10hours, performed three times a week. This mode allows night time treatment and is appropriate for working patients
  • Continuous ambulatory peritoneal dialysis is performed daily for 24hours with four exchanges daily. The patient can remain active during the treatment.
  • Continuous cyclic peritoneal dialysis may be used if the two other modes fail to improve creatinine clearance. Dialysis takes place at night; the last exchange is retained in the peritoneal cavity during the day, then drained that evening.

Advantage of peritoneal dialysis

Advantages of peritoneal dialysis include a lack of serious complications,  retention of normal  fluid and electrolyte balance, simplicity, reduced cost, patient independence and a reduced need for heparin administration

Complication of peritoneal dialysis

This includes hyperglycemia, constipation and inflammation or infection at the catheter site. Also, this method carries a high risk of peritonitis.

Renal transplantation:

This surgical procedure allows some patients with end-stage renal disease to live normal and in many cases longer lives

  1. Histocompatibility must be tested to minimize the risk of transplant rejection and failure. Human leukocyte antigen(HLA) type, mixed lymphocyte reactivity, and blood group types are determined to assess histocompatibility
  2. Renal transplant material may be obtained from a living donor or a cadver.
  3. Three types of graft rejection can occur

Renal graft rejection types

1. Hyperacute (immediate) rejection

This results in graft loss within minutes to hours after transplantation.

Signs of hyperacute rejection

  • Acute urine flow cessation and bluish or mottled kidney discoloration are intraoperative signs of hyperacute rejection
  • Postoperative manifestations include kidney enlargement, fever, anuria, local pain, sodium retention, and hypertension

Treatment for hyperacute rejection

This is immediate nephrectomy

2. Acute graft rejection

  1. Acute rejection may occur 4-60days after transplantation 

3. Chronic graft rejection

  • Chronic rejection occurs more than 60 days after transplantation
  • Signs and symptoms include low-grade fever, increased proteinuria, azotemia, hypertension, oliguria, weight gain and edema
  • Treatment may include alkylating agents, cyclosporine, antilymphocyte globulin and corticosteroids. In some cases, nephrectomy is necessary

Complications of chronic kidney disease

Complications of CKD include;

  • Infection, diabetes, hepatitis and leukopenia, resulting from immunosuppressive  therapy
  • Hypertension resulting from various causes
  • Cancer (e.g, lymphoma, cutaneous malignancies, head and neck cancer, leukemia, colon cancer)
  • Pancreatitis and mental and emotional disorders(e.g suicidal tendencies, severe depression, brought on by steroid therapy)

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