Chronic renal failure is irreversible deterioration in renal function. Impairment in excretory, metabolic and endocrine functions of the kidney leads to the development of uremia. These patients usually have bilateral small kidneys. Renal failure of more than six months are termed as chronic.

Etiology:
Chronic renal failure may be caused by any condition that destroys the normal structure and function of the kidney. Common causes are;

1. Congenital and inherited diseases:
• Polycystic kidney disease (infantile or adult)
• Alport’s syndrome
• Congenital hypoplasia

2. Vascular diseases
• Arteriosclerosis
• Vasculitis (PAN, SLE, scleroderma)

3. Glomerular diseases
• Proliferative Glomerulo nephritis
• Crescentic Glomerulo nephritis
• Membranous Glomerulo nephritis
• Mesangio capillary Glomerulo nephritis
• Glomerulosclerosis
• Secondary Glomerulo nephritis

4. Interstitial diseases:
• Chronic Pylonephritis
• Vesico- ureteric reflux
• Tuberculosis
• Analgesic nephropathy
• Nephrocalcinosis
• Schistosomiasis

5. Obstructive uropathy
• Calculus
• Retroperitoneal fibrosis
• Prostatic hypertrophy
• Pelvic tumors

6. Systemic diseases
• Diabetic nephropathy
• Gout
• Amyloidosis
• Multiple myeloma
• Radiation nephropathy

Pathogenesis:
Chronic renal failure is due to progressive destruction of nephrons. As the nephrons are destroyed, the parenchyma shrinks and it is replaced by fibrosis. The remaining nephrons undergo hypertrophy. This gives an appearance of granular contracted kidney. But the renal functions are maintained by the hypertrophied nephrons. Since the concentrating function is impaired, Polyuria with urine of specific gravity around 1.010 (specific gravity of glomerular filtrate) occurs. Defective renal function leads to secondary hypertension, which in turn leads to deleterious influence on the kidney, brain, and heart. There is accumulation of phosphates, parathyroid hormone, urea, creatinine, guanidine, phenols and indoles in the body fluids.

Clinical features:
Early phases of the disease are asymptomatic, since the kidney has considerable reserve function. Symptoms and biochemical abnormalities are evident only when the renal function has deteriorated to less than 35% of the normal. When the renal function is between 35% and 25% of the normal, symptoms like pallor, tiredness, and nocturia are evident. The blood urea and serum creatinine are elevated and the serum bicarbonates are reduced.when the renal function falls to 25-15% of the normal symptoms like fatigue, nausea, anemia, impotence, metabolic acidosis and the bone pains may develop. When the renal function is below 15% the full-fledged uremic syndrome develops. This includes the following symptoms.

• Vague ill-health
• Generalized weakness and lack of energy
• Breathlessness on exertion
• Anorexia
• Hiccough
• Nausea and vomiting which are aggravated in the morning
• Disordered intestinal motility
• Headache
• Visual disturbances
• Pruritus ( due to calcium deposition)
• Pallor
• Pigmentation ( due to calcium deposition)
• Loss of libido
• Anemia (due to reduced dietary intake of iron and other haematinics due to anorexia and dietary restrictions, impaired intestinal absorption of iron, diminished erythropoiesis due to toxic effects of uremia on marrow precursor cells, reduced red cell survival and increased blood loss due to capillary fragility and poor platelet function.)
• Metabolic bone disease (or Renal osteodestrophy which include osteomalacia, osteoporosis, osteitis fibrosa or rickets. Osteomalacia results from diminished activity of the renal 1-hydroxylase enzyme with consequent failure to convert Cholecalciferol to its active metabolite 1, 25 –dihydroxy- cholecalciferol. Deficiency of 1,25-dihydroxy- Cholecalciferol leads to diminished intestinal absorption of calcium, hypocalcaemia and reduction in the calcification of osteoid. Osteitis fibrosa results from secondary hyper-parathyroidism. Osteoporosis is related to mild malnutrition.)
• Neuropathy ( demyelination of medullated fibres leads to neuropathy. Sensory neuropathy leads to parasthesiae and motor neuropathy is presented as foot drop)
• Myopathy ( due to poor nutrition, hyperparathyroidism, vitamin D deficiency and disorders of electrolyte metabolism)
• Endocrine abnormalities ( Amenorrohea, infertility, secondary hyperparathyroidism)
• Hypertension and atherosclerosis
• Acidosis
• Susceptibility to infection ( both cellular and humoral immunity are impaired . urinary tract infections are very common)
• Insomnia
• Reversal of sleep rhythm
• Convulsions
• Coma
• Cardiac failure
• Pericarditis
• Myocardiopathy
• Red eye ( due to conjunctival congestion and calcium deposition)
• Band keratopathy ( due to calcium deposition in cornea)
• Hypertensive retinopathy
• Kussmaul’s respiration
• Uremic lung ( increased pulmonary capillary permeability leading to transudation of fluid )

Investigations:
Urine:
Volume is high (2-3 litres in 24 hours). Mild proteinuria. Fixed specific gravity around 1.010 and an osmolality of 300 m Osm/ Kg. The presence of broad casts in urine confirms the chronic nature of the illness.
Blood:
Blood urea, serum creatinine, serum uric acid and inorganic phosphates are elevated. Calcium and bicarbonate levels are reduced.
Radiology:
Plain X-ray of the abdomen may help if the renal size is small.
Ultrasonography:
This is helpful in assessing the renal size. Renal biopsy helps to arrive at the precise histological diagnosis.

Management:
The treatment of chronic renal failure is influenced by several factors and also the stage at which the patient is first seen. The reversible complicating factors
(Hypertension, urinary tract infection, urinary tract obstruction, reduced renal perfusion, septicemia, infection which increase urea production and nephrotic medications) have to be identified and treated.
Dietary restrictions:
About 1700 Kcal have to be provided by a diet containing carbohydrates (250g) and fats (60g). Proteins should be restricted to about 40 g per day.

Water intake:
It is advisable to have urine out put of 2.5 to 3 litres per day by appropriate increase in water intake if the patient can tolerate it. A fluid intake of 3 litres per day is desirable. Fluid restriction is necessary only when the GFR is less than 5 ml/minute or the cardiac failure is present.

Electrolytes:
In the absence of oedema, cardiac failure or hypertension, sodium restriction is contraindicated. Patients with salt-losing nephropathy readily become depleted of sodium and water, particularly if they are vomiting. When this occurs fluid and electrolytes must be given intravenously. Generally in patients with glomerular disease and hypertension, a diet containing about 80-100 mmol of sodium per day (“ no added salt-diet”) should be prescribed.
When the creatinine clearance has fallen to less than 10 ml/min, potassium restriction is often required and is achieved by advising the patient to avoid high potassium foods like bananas, tomatoes, coffee and chocolate.

Hematological problems:
Symptomatic anemia with hemoglobin less than 7 g/dl or PCV less than 18% has to be corrected by packed cell transfusions. Other factors, which aggravate anemia such as nutritional inadequacy and blood loss, should also be corrected.

Hypertension:
The diastolic blood pressure must be maintained at 90 mmHg. Over-zealous treatment must be avoided.

Renal osteodestrophy:
Low phosphorus diet should be advised (egg, milk and milk products should be avoided). Supplements of calcium with Vitamin D have to be given to elevate calcium levels and abolish symptoms of hypocalcaemia.

Replacement of renal function:
The excretory function of kidney can be partially replaced by dialysis. But the endocrine and metabolic functions can only be achieved by successful renal transplantation.

Haemodialysis:
This should be started when the symptoms of uremia have become troublesome, despite adequate medical treatment, preferably before the patient develop serious consequences of uremia. First an arteriovenous fistula is created in the forearm, this results in distention and thickening of the vein wall which allows the repetitive insertion of needles for vascular access for heamodialysis. This is carried out for 3-5 hours 3 times weekly. Most patients notice a gradual reduction of their uremic symptoms during the first 6 weeks of treatment. They can lead relatively normal and active lives, and prolonged survival in excess of 20 years is now regularly reported.

Continues ambulatory peritoneal dialysis:
It is a form of long- term dialysis involving insertion of a permanent intraperitoneal catheter into the abdominal cavity. Normally 2 liters of sterile isotonic dialysis fluid are introduced and left for a period of approximately 6 hours. The fluid is then drained and fresh dialysis fluid is introduced. This cycle is repeated 4 times daily, during which time the patient is fully mobile and able to undertake normal daily tasks. It is useful for the treatment of children, elderly patients with cardiovascular instability and in patients with diabetes mellitus.

Renal transplantation:
Many metabolic abnormalities of uremia can be corrected by renal transplantation. The graft is taken from a cadaver donor or from a sibling or a parent. ABO compatibility is essential and it is customary to select donor kidneys on the basis of HLA (Human Leucocyte Antigen) compatibility. The 3-year graft survival is now in the region of 70-80%, while 3-year patient survival is approximately 90%.

Medicinal management:
AMMONIUM CARB:
Heaviness in all organs, swelling of glands, acid reactions; prostration; frequent desire to urinate with tenesmus; urine white, scanty, bloody copious turbid and fetid.

ARSENIC ALB:
Urine is scanty, burning involuntary. Bladder as if paralyzed. Albuminuria. Nephritis. Uremia. Atony of bladder in old persons. Epithelial cells cylindrical clots of fibrin and globules of pus and blood. Feeling of weakness in abdomen after urination. Retention of urine, as if the bladder were paralyzed after childbirth. Urine black as if mixed with dung. Dysuria.

AURUM MET:
Painful retention of urine, with urgent inclination to make water, and pressure on the bladder. Frequent emission of watery urine. Urine turbid, like buttermilk, with thick mucus-like sediment.

CICUTA:
Frequent micturition; the urine is propelled with great force. Retention of urine. Convulsions with violent distortion of body.

CUPRUM MET:
Suppression of urine. Passes clear watery urine during or after spasms. Urgent desire to urinate with scanty emission. Frequent emission of fetid, viscid urine, Burning shootings in the urethra, during and subsequent to the emission of urine. Wetting the bed at night.

CUPRUM ARS:
Diabetes. Kidney inefficiency and uremia. Garlic odor of urine. Urine of high specific gravity increased, Contains acetones and diacetic acid.

GLONOINE:
Increased secretion of pale (albuminous) urine; has to rise frequently during the night, and must pass large quantities of albuminous urine. Tubal nephritis, with headache, brought on by walking in the sun; numbness in arms and hands alternating with intense tingling. Inclination to deep respiration.

HYDROCYANIC ACID:
Heart’s action diminished. Pulse accelerated, soft. Stagnation of circulation of heart and lungs. Palpitation with indescribable anguish and dyspnoea. Depression of sensibility, convulsion and paralysis. Slow moaning breathing , rattling in trachea , paralysis of larynx or sudden paralysis of heart.

NICOTINUM:
Paralysis of diaphragm. Indifference. Want of reaction, cold forehead, thirstlessness. Serous transfusions in intestines without diarrhea. Want of secretions in kidney and liver.

OPIUM:
Scanty, deep coloured (dark brown) urine, with sediment like brick dust. Retention of urine. Coma. Insomnia. Intermittent respiration.

PHOSPHORUS:
Urine turbid, brown, with red sediment. Uremia with acute atrophy of brain.

PICRIC ACID:
Complete anuria, nephritis with profound weakness.

PLATINA:
Red urine with a white cloud, or else which becomes turbid, and deposits red sediment. Slow but frequent emission of urine.

TEREBINTHINA:
Pressure in the kidneys when sitting, going off during motion. Sensation of heaviness and pain in region of kidneys. Transient movement in region of bladder during stool as if bladder were suddenly distended and bent forward. Frequent desire to urinate. Violent burning drawing pain in region of kidneys. Spasms from any attempt to urinate. Suppressed secretion of urine. Urine smelling strongly of violets; deposit of mucus, or thick, muddy deposit. Thick, slimy, yellowish white sediment in urine. Much blood with very little urine and constant painful Dysuria. Burning sensation, incisive pains, and spasmodic tenesmus of bladder.

Probable miasm:Sycotic

Rubrics related to uremia:

Boger’s repertory:
1. Sensation and complaint in general : Uremia
2. Urine: Albuminous
3. Urine : Flocculent and filamentous
4. Urine : Turbid, cloudy

Boericke’s repertory:
1. Generalities: Kidney disease from
2. Urinary system; Kidney: Acute and subacute paranchymatous nephritis; concomitants; uremic symptoms
3. Urinary system: Symptoms of uremia: In general
4. Urinary system: Symptoms of uremia: coma
5. Urinary system: Symptoms of uremia: convulsions
6. Urinary system: Symptoms of uremia: headache
7. Urinary system: Symptoms of uremia: vomiting

Knerr’s repertory:
1. Urinary organs: Kidney : Dropsy: Affections with
2. Urinary organs: Kidney : Anasarca, especially in albuminuria, after
3. Urinary organs: Kidney : Dysuria,
4. Urinary organs: Kidney : Nephritis after
5. Urinary organs: Kidney: Prostration with
6. Urinary organs: Kidney: Pain; albuminuria with

Phatak’s repertory:
1.Kidneys: Contracted
2. Urine: Suppressed: Convulsions with

Synthesis repertory:
1. Generals: Uremia
2. Kidney: Pain
3. Kidney: Suppression of urine; convulsions with
4. Urine: Casts, containing
5. Urine: Casts, blood
6. Urine: Casts, epithelial
7. Urine: Casts, fat drops, with
8. Urine: Casts, fibrous
9. Urine: Casts, granular
10. Urine: Casts, hyaline
11. Urine: Casts, mucous
12. Urine: Casts, tubes of
13. Urine: Casts, ureate

Reference:
1. Davidson’s Principle and Practice of Medicine 17th edition
2. K.V. Krishnadas’s Textbook of Medicine 3rd edition
3. Raue’s Special Pathology
4. Descriptive Medicine by Kichlu and Bose
5. Synthesis by Dr.Fredericke Schroyens
6. Boenninghausen’s characteristics Materia Medica and Repertory by C.M.Boger
7. Phatak’s Repertory
8. Knerr’s Repertory
9. Boericke’s Repertory