ACUTE & CHRONIC RENAL DISEASE

Prof. Sir J.W. Acheampong

Functions of the Kidney

1) Retention of substance vital to body economy
(a) Reabsorption of Glucose, Amino acids, Phosphates (b) Reabsorption of Na + H20

2) Excretion of waste metabolic products

(a) End products of metabolism especially those of protein and Amino acids (Endogenous) Urea Creatinine Uric acid (b) exogenous products (such as drugs

3) Hormonal & Metabolic functions:

(a) The JGA secrete renin (b) Erythropoietin (c) Hydroxylase 25-hydroxycholecalciferol to 1,25 dihydroxycholecalciferol. Prostaglandins (PGE2 and PGI2) Secrets glandular Kallikrein, an enzyme which generates vasodilator peptides, - bradykinin and Kallikrein, from Kininogen precursors

Definition normal (800 2000 ml).

-Oliguria < 400 ml. -Anuria 100 ml, Complete Anuria No urine -Polyuria increase vol. of urine -Azotemia refers to the retention of nitrogenous waste products as renal insufficiency develops. -Uraemia refers to the more advanced stages of progressive renal insufficiency, when the complex, multiorgan system derangements become clinically manifest.

(a) Uraemia involves more than excretory failure

alone (b) (b) Impaired metabolic and Endocrine functions leading to -Anaemia -Malnutrition -Impaired metabolism of carbohydrates, fats and proteins defective utilization of energy -Metabolic bone disease

Acute Renal Failure (ARF)

Is characterised by an acute and usually reversible deterioration of renal function which develops over a period of days or weeks and results in uraemia. Many of the disorders giving rise to ARF carry a high mortality, but if the patient survives, renal function usually returns to normal or near normal.

CLASSIFICATION OF ARF
1) Prerenal

2) Renal (intrinsic renal ARF) - Preglomerular - Glomerular - Postglomerular tubules + interstitium are primarily involved 3) Post renal - intraluminal (papilla or stone) - Luminal (within the wall as in schistosomiasis and TB - Extra luminal e.g.. Ca of cervix.

CLASSIFICATION OF ACUTE RENAL FAILURE

Prerenal ARF: The kidneys are inadequately perfused and the GFR greatly diminished. This may be due to cardiac failure, vascular disease limiting renal blood flow, or underfilling of the vascular bed due to hemorrhage, severe fluid depletion or vasodilatation resulting from sepsis. Renal causes of ARF include diseases of the renal arterioles such as vasculitis or microangiopathic haemolytic states; rapidly progressive (crescentic) glomerulonephritis; injury to tubular cells (acute tubular necrosis) by toxins or ischaemia; intraluminal obstruction of nephrons from precipitation of crystals or protein; and acute interstitial nephritis due to infections or drug reactions.

CLASSIFICATION CONTD

Postrenal

ARF is caused by obstruction of the urinary tract at any point in its course.

Prompt identification of the cause of prerenal or postrenal ARF and institution of appropriate treatment will often restore renal function. The longer the period of inadequate perfusion or obstruction, the more likely it is that actual damage to kidney tissue will occur.

PRERENAL ACUTE RENAL FAILURE: THE MOST IMPORTANT CAUSES

Reduced circulation blood volume Haemorrhage from any cause, including

complications of pregnancy, trauma and gastrointestinal bleeding, Loss of plasma as in burns and crushing injuries
Sodium and water depletion:

- From the gastrointestinal tract in severe vomiting, diarrhoea, acute intestinal obstruction, paralytic ileus, pancreatitis, fistulae - In urine due to excessive treatment with diuretics, diabetic ketoacidosis - From the skin due to sweating

Reduction of cardiac output and myocardial failure (cardiogenic shock), or an increase in the size of the vascular bed (septicaemia)
Intravascular haemolysis

Rhabdomyolysis (breakdown of skeletal muscle), due to the toxic effects on the kidney of released globins
Diseases of the major renal vessels which result in renal underperfusion e.g. thrombosis of the arteries, occlusive embolus of the aorta or renal arteries, or aortic aneurysm.

DIAGNOSIS OF PRERENAL ACUTE RENAL FAILURE

A compatible history

The clinical findings

A progressive increase in blood urea and plasma

creatinine Urine osmolality > 600 mOsm/kg; urine sodium <20 mmol/l; urine/plasma urea ratio of > 10:1 The urinary findings depend on the kidneys ability to respond to inadequate perfusion by intense conservation of sodium and water. They will therefore not be found in patients with pre-existing renal impairment..

Clinical Features These reflect the causal condition together with features of rapidly developing uraemia. - Causal conditions such as - Trauma - Septicaemia (S. typhi), (obstetric disorders + infection) - Diarrhoea and vomiting disease, (cholera) Oliguria (50 500ml dly) Anuria (rare)

Clinical Features Contd

- Normal or increased urine volume but the quality is very poor due to a low GFR and a gross reduction of tubular function. - The rate at which the plasma urea + creatinine increases is determined by the rate of tissue breakdown. - In severe infection, major surgery or trauma dly increase in plasma urea > 5mmol/ol. - Disturbances of H20, electrolyte and acid base balance. - Hyperkalaemic (K>6 mmol/) ventricular Arrhythmias. - Dilutional hyponatraemia

Clinical Features Contd

Anorexia Nausea + vomiting Apathy followed by mental confusion Muscular twitching, fits, drowsiness, coma Bleeding episode Increased respiratory rate (due to acidosis) Pulmonary oedema Respiratory infection Anaemia blood loss (platelet function disorder coagulopathy) haemolysis decrease erythropoeisis erythropoetin marrow suppression.

DIAGNOSIS
A careful history is essential. - Renal colic suggests an obstructive cause - Major illness vasomotor nephropathy with or without tubular necrosis. - History of taking drugs herbal mixtures. (e.g, Nim tree leaves) - Acute Haemolysis (look for G6PD deficiency) induced by infection, sulphonamides, Nitrofurantoin, paraminosalicylic and dapsone, and phenytoin.

MANAGEMENT

Emergency resuscitative measures

Hyperkalemia (Plasma K+> 6mmol/l) must be counteracted and corrected to prevent life threatening cardiac arrythmia. - Connect ECG monitor arrythmia - Reliable (Iv) access in a large vein to be established femoral rein, jugular vein. - Give (i) calcium gluconate (10ml, 10%) membrane stabilising effect of the heart. - Give 50ml of 50% dextrose +12 units soluble insulin Rapid reduction of plasma (K+). Potassium intracellular space (iv) NaHC03 to correct acidosis K+ Give calcium resonium (Exchange resins) orally and / or rectally. Dialysis definite treatment in many cases.

GENERAL MANAGEMENT
IN ESTABLISHED ARF
1) 2) 3)

4) 5) 6)

Control fluid and electrolyte balance. Input = output + 6001000 ml (insensible fluid loss) Prevent hyperkalaemia fruits (bananas + coconut, nuts, etc) Ensure an adequate caloric intake, maintain Nutrition 2000 3000 Kcal. protein 0.5-0.6 /kg: Energy from fat & KHO + Concentrated dextrose via central venous line. Minimize accumulation of waste products urea, creatinine, electrolytes - estimated regularly. Protect patient from infection. Cultures of blood, urine & wound - carried out regularly. Liquid feeding via a nasogastric tube may be helpful.

CLINICAL PICTURES OF REVERSIBLE ARF

Initial insult (Infective shock) BP pulse Urine initially concentrated Onset phase
Oliguric phase

- Established ARF urine dilute - Low urine output up to 21 days urine dilute patient uraemic & acidotic

Recovery phase - (3 4) days - Polyuria (3 5) - salt + water depletion - hypokalaemic

CHRONIC RENAL DISEASE

Chronic renal disease (CRD) is a pathophysiologic process with multiple etiologies, resulting from progressive nephron loss and function, and frequently leading to endstage renal disease (ESRD).

ESRD
Represents a clinical state or condition in which there has been an irreversible loss of endogenous renal function, of a degree sufficient to render the patient permanently dependent upon renal replacement therapy (dialysis or transplantation) in order to avoid life-threatening uraemia.

URAEMIA
Is the clinical and laboratory syndrome, reflecting dysfunction of all organ systems are as a result of untreated or undertreated acute and chronic renal disease.

Some causes of chronic renal disease in Africa

(1) Glomerulonephritis

(2) Pyelonephritis (including schistosomiasis and

other uropathies, vesico-vaginal fistulae and vesico-ureteric reflux) (3) Amyloid kidney (4) Diabetic Nephropathy (5) Hypertension

Clinical Abnormalities in uraemia

1) Fluid and electrolyte disturbances Vol expansion and contraction Hypernatremia and hyponatremia Hyperkalaemia and hypokalaemia Metabolic acidosis Hyperphosphatemia Hypocalcemia

2) Endocrine metabolic disturbances - Secondary hyperparathyroidism - Osteomalacia - Carbohydrate intolerance - Hyperuricaemia - Hypertriglyceridaemia - Decrease high density lipoprotein level (HDL) - protein calorie malnutrition - Infertility and sexual dysfunction - Amenorrhoea

Neuromuscular disturbances
Fatigue Sleep disorder Lethargy Asterixis Peripheral neuropathy Restless legs syndrome Paralysis Seizures Coma Muscle cramps Myopathy

Cardiovascular and pulmonary disturbances

HPT CHF Pericarditis Cardiomyopathy Uraemic lung Accelerated artherosclerosis Hypotension and Arrythmias

Dermatologic disturbances
Pallor Hyperpigmentation Pruritus Ecchymoses Uraemic frost

Gastrointestinal disturbances
Anorexia Nausea and vomiting Uraemic foetor Gastro-intestinal bleeding Peritonitis

Haematologic and immunologic disturbances

Anaemia Bleeding diathesis Increased susceptibility to infection splenomegaly and hypersplenism,leucopenia.

Signs and symptoms of uraemia

Vague ill-health Generalised weakness and lack of energy Breathlessness on exertion Anorexia Nausea + Nausea and vomiting particularly in the mornings Disordered intestinal motility Headaches

Signs and symptoms of uraemia (cont.)

Visual disturbances Pruritus Pallor Pigmentation Loss of libido

RENAL OSTEODYSTROPHY
Osteomalacia Osteitis fibrosa Osteoporosis Osteosclerosis

MANAGEMENT OF CHRONIC RENAL DISEASE

Investigation to determine the underlying renal disease and to detect any reversible factors Measures designed to limit adverse effects of loss of renal function and when possible to prevent further renal damage

In patients with progressive destruction of renal tissue there comes a point when supportive measures in form of either dialysis or transplantation are required

Management of CRD (cont.)

Hypertension must be controlled (diastolic pressure about 90 mmHg) CHF- treated along the usual lines

Diet Restrict protein diet (0.5 0.6 g/kg) = 40g/day Adequate carbohydrate (250g) Fat (60g) Kcal at least 1800 per day

Management of CRD (cont.)

Loss of salt and water: A diet containing about 80- 100 mmol of sodium per day( no-added-salt diet) is prescribed. The uncontrolled use of drugs: Avoid tetracycline, digitalis and other drugs excreted by the kidney.

Phosphate retension leads to calcium and phosphate deposition in the kidney and other soft tissues. Aluminium hydroxide gel will bind phosphate in the intestine and prevent this process causing more renal damage. NB. CaCo3 can be used. Retained PO4 is a major cause of the development of secondary hyperparathyroidism in CRD. Urinary tract infection may further worsen renal function.

Patients should be advised to drink enough to keep up with their urinary output ( 2L per day). An increased washout of urea Reducing the likelihood of volume depletion Producing more frequent urination which may prevent infection Cave fluid retention when GFR is 5ml/min or CHF.

The challenge of dialysis and transplantation

Hemodialysis Peritoneal dialysis Continuous ambulatory peritoneal dialysis (CAPD) Transplantation

THANK YOU