Chronic Renal Failure (CRF) OR CRD/CKD

Chronic renal disease is a destruction of neph­rons of the kidneys due to several causes. The damage to renal structure and function is irr ­versib This results in uremia which leads to dysfunction of several organs. Chronic kidney disease (CKD) is defined as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m²for >3 months. The destruction of kidney is a chronic process of more than 3 months.

Stages of Chronic Renal Disease/Chronic Kid­ney Disease (CKD)

• Stage 1
  • Kidney damage with normal or in­creased GFR – 90 ml/min/1.73 m²
• Stage 2
  • Kidney damage with decreased GFR­60-89
• Stage 3
  •  Moderately decreased GFR 30-59
• Stage 4
  • Sftverely decreased GFR 15-29
• Stage 5
  • Renal failure GFR < 15

Risk factors for CRD/CKD

• Family history of renal disease
•  Hypertension
• Diabetes
• Autoimmune disease
• Old age
• History of acute renal failure
• Smoking
• Low income/education
• Ethnic minority status
• Evidence of kidney damage
• Proteinuria, abnormal urinary sediment, urinary tract structural abnormalities.
• A typical cause of chronic renal disease (CRD) is dia­betic nephropathy.
• The first feature of CRD is usually albuminuria. Albumin-specific dipstick measurement of albumin to creatinine ratio in the first morning urine spot sample if more than 17 mg albumin per gram of serum crea­tinine in adult males and more than 25 mg albumin per gram of creatinine in adult females signifies CRD.

History of CRF

• Oliguria, nocturia, polyuria, change in urinary frequency
• Hematuria
• Bone disease
• Fatigue, depression, weakness
• Pruritus, tremor
• Metallic taste in mouth, uremia
• Anorexia, nausea, vomiting
• Obesity
• Dyspnea
• Hypertension
• Poorly controlled diabetes with retinopathy, neuropathy
• Hyperlipidemia
• Claudication

Common causes of chronic renal disease and presentations

• Diabetic kidney —>
  • History of diabetes, proteinuria, retinopathy
• Hypertension —->
  • High blood pressure, Family history, Normal urinary findings
• Non-diabetic glomerular disease —– >
  • Nephritic, Nephrotic
• Cystic kidney disease —–>
  • Urinary tract symptoms, abnormal urinary sediments, abnormal imaging findings
• Tubulointerstitial disease —–>
  • UTI, Drugs, tubular syndromes, abnormal urine findings

Pregnancy Considerations in CRF

• Renal function in CKD may deteriorate during pregnancy.
• Creatinine >1.5 and hypertension are major risk factors for worsening renal function.
• Increased risk of premature labor, preeclampsia, and/or fetal loss

Physical Examination in Chronic Renal Failure (CRF)

• Complete physical plus ophthalmic exam; assess volume status (e.g., blood pressure with orthostatics; edema; jugular venous distention; weight)
• Skin: Sallow complexion, uremic “frost”
• Ammonialike odor (uremic fetor)
• Cardiovascular: Assess for mumurs, bruits, pericarditis
•  At GFR (Glomerular Filtration Rate) less than 60 ml/ min all organ systems are affected.
• There is anaemia, loss of energy, decreasing appe­tite, abnormal calcium and phosphorus metabolism, metabolic bone disease, sodium, water, potassium and acid-base disturbances.
• At GFR < 15 ml/min the patient is not able to lead a regular life and may be in a uremic state needing’ urgent renal replacement therapy (dialysis etc.)

Genetics of CRF —

• There may be a monogenic inheritance,
• autosomal dominance or
• polymorphism of ACE (Angiotensin Con­verting Enzyme) genes.

Cockcroft-Gault Equation for creatinine clear­ance

• . Creatinine clearance ml/min in men = (140-age) X body weight in Kg. / 72 x Pcr mg/dl
• Creatinine clearance ml!min in women (140-age) X body weight in Kg. X 0.85  /  72 x Pcr mg/dl

UREMIA IN CRF

• Azotemia is retention of nitrogenous waste products due to renal insufficiency.
• Uremia is progressive renal insufficiency with multi­organ involvement.
• In uremia there is anorexia, malaise, vomiting, head­ache.
• In uremia there is toxicity due to urea, urates, hippurates, polyamines, phenols, benzoates and in­doles.
• As a result there is :
• Anaemia Malnutrition
• Impaired metabolism of carbohydrates, fats and proteins
• Loss of energy Metabolic’ bone disease
• Increased levels of :
  • PTH – parathyroid hormone
  • Insulin ,
  • Glucagon
  • Luteinizing hormone
  • Prolactin
• Decreased levels of :
  • EPO – erythropoietin
  • 1,25, dihydroxycholecalciferol
• Electrolyte abnormalities

Fluid, Electrolyte and Acid Base Disturbance Sodium and water

• There is increase of sodium and water in the body.
• There is sodium retention.
• There is extracellular fluid volume expansion (ECFV).
• Therefore, there is hyper­tension.
• There is weight gain.
• There is volume deple­tion only if there is vomiting, diarrhea, sweating, fe­ver or diuretic administration.

Treatment

•  Diuretics – loop diuretics, metolazone ‘Q/ Restricted salt intake
• Dialysis
• For volume depletion – normal saline infusion

Potassium

• There may be hypokalemia due to excretion of potas­sium in GIT.
• – There may be hyperkalemia due to constipation, pro­tein catabolism, hemolysis, haemorrhage, RBC trans­fusion, metabolic acidosis.
• Drugs which may cause hyperkalemia are ACE inhibi­tors, ARBs, potassium sparing diuretics, Beta blockers and NSAIDs.
• hyperkalemia is more common in CRD than hypokale­mia.

Metabolic acidosis in CRF

• ~There is metabolic acidosis because of reduced abil­ity to produce ammonia.
• Hyperkalemia in CRD decreases ammonium excre­tion. This results in metabolic acidosis.
• In diabetics there is hyperkalemia, metabolic acido­sis-renal tubular acidosis, hyporenin hypoaldostero­nism.
• Treatment of hyperkalemia improves acidosis.

Treatment of Hyperkalemia and Acidosis

• Potassium binding resins
• Restriction of potassium salts
• Loop diuretics
• For acidosis NAHC0₃ may be given if pH <7.35 .

Bone disease and Disorders of Calcium and Phos­phate

• High bone turnover and high PTH levels result in sec­ondary hyperparathyroidism and osteitis fibrosa.
• Low bone turnover and low PTH level result in osteo­malacia.
• Decreased GFR causes decreased excretion of phos­phate and retention of phosphates.
• This causes increased PTH and lowering of calcium, decrease of calcitriol resulting in hypocalcemia and bone diseases, osteomalacia, vitamin D deficiency, metabolic acidosis.
• This causes bone pains, fractures, incapacity, diffi­culty in walking and movements.
• Calciphylaxis is metastatic calcification of soft tissue and blood vessels.

Treatment

• Calcitriol
• Avoid aluminium compounds Calcium acetate
• Calcium carbonate and Sodium phosphate binding agents.

Cardiovascular abnormalities in CRF

• Ischemic heart disease
• Hypertension
• Left ventricular hypertrophy
• Congestive heart failure Pulmonary edema
• Uremic pericarditis and cardiac tamponade, hem­orrhagic pericardial effusion
• Dyslipidemias
• Hyperhomocysteinemia.

Treatment

• For hypertension:
  • ACE I and ARB’s if serum crea­tinine less than three
  • Nifedipine, hydralazine, diltiazem, minoxidil.
• For dyslipidemias :
  • Statins, gemfibrozil
• For hyperhomocystinemia –
  • Vitamins, folate supplementation
• Control of diabetes:
  • Metformin is not used Insulin levels are increased in CRD
• For Pericarditis :
  • Dialysis, pericardiectomy, as­piration of fluid.

Hematological abnormalities Anaemia due to :

• · Insufficient EPa (Erythropoietin)
• · Iron and folate deficiency
• · Hyperparathyroidism
• · Chronic inf~ction
• · Hemoglobinopathies
• · Coagulation abnormalities
• · Increased bleeding time
• · Increased platelet aggregation
• · Thromboembolic complications.

Treatment

• EPa (Erythropoietin) is given 50-150 units /kg/ week subcutaneous
• Side–effect of EPa – Hypertension, malignan­cies
• Iron supplementation Vitamin B_I2, folate Anticoag u lant prophylaxis.

Neuromuscular abnormalities in CRF

• Central and Peripheral neuropathy Memory impairment
• Insomnia
• · Asterixis
• · Irritability
• · Muscle twitching
• · Seizures
• · Restless legs syndrome
• · Coma

Gastrointestinal abnormalities in CRF

• · Uremic fetor or odour or breath
• · Gastritis
• · Peptic disease
• · Abdominal pain, nausea, vomiting
• · Pancreatitis
• · Anorexia
• · Hiccups.

Endocrine and Metabolic disturbances

• · Impaired glucose metabolism
• · Plasma insulin levels are elevated
• · Amenorrhoea
• · Growth retardation.

Dermatologic abnormalities

• · Itching – Uremic pruritus
• · Pallor – Skin necrosis

Management Treatment of CRD

• · Control hypertension – ideal blood pressure 125/ 75
• · Control diabetes – preprandial glucose 90 – 130 mg/dl and HBA_1C level <7.2%
• · Treat infections
• · Avoid nephrotoxic drugs
• · Estimation of plasma creatinine, GFR
• · Management of electrolyte imbalance
• · Management of acid-base disturbance
• · Ultrasound for kidney size, renal masses
• · Treat obstructive uropathy
• · Voiding cystourethrography and management
• · Renal biopsy and specific management
• · Management of bleeding
• · If kidney size <8.5 cm irreversibility of disease
• · Protein restriction to 0.6 g/kg/day
• · Dialysis
• · Kidney transplantation.

Indications for Dialysis in CRF

• Pericarditis
• Neuropathy due to uremia
• Encephalopathy
• Muscle irritability
• Anorexia, nausea, vomiting Fluid electrolyte abnormalities Severe volume overload Non-responsive hyperkalemia Progressive metabolic acidosis Asterixis
• Serum creatnine >8 mg/dl.

Indications for Kidney transplantation in CRF

• Irreversible ESRD (End Stage Renal Disease) Good antigenic match with donor
• First degree relative donor
• Primary transplantation.