Renal Failure

Types

• Acute

• Chronic

Acute renal failure

• Sudden onset with oliguria/anuria

• Rapid rise in BUN and S Creatinine

RENAL DISEASE – CLINICAL FEATURES

• Azotaemia = BUN , Creatinine - biochemical abnormality

• Pre renal- due to renal hypoperfusion ( shock, haemorrhage, CCF). No parenchymal renal disease.

• Renal – due to renal parenchymal disease.• Post renal – due to obstruction to urine outflow

below kidney.

• Uraemia = azotemia + S/S of renal failure

Types

• Pre-renal

• Intra-renal

• Post-renal

Pre-renal

• Inadequate blood flow to kidney– Hypovolemia– Renal artery stenosis– Congestive cardiac failure– Intrarenal small vessel disease– Drugs ( NSAIDs, ACE inhibitors )

Intra-renal

• Glomerulonephritis

• Interstitial nephritis

• Toxin induced

• Pigment induced

Post-renal

• Intra – renal obstruction

• Extra – renal obstruction

Pathogenesis

• ARF leads to acute tubular necrosis

• Hypoxic injury

Renal Tubular Injury in ATN

Loss of polarity and brush border

Normal epithelium with brush border

Cell death -apoptosis and necrosis

Sloughing of dead and viable cells - luminal obstruction

Spread and de-differentiation of viable cells

Proliferation, differentiation and reestablishment of polarity

Normal epithelium with brush border

Urinary abnormalities

• ATN – Granular, epithelial casts, urine osmolality < 350 mOsm/L

Other abnormalities

• Hyperkalemia

• Azotemia

• Metabolic acidosis

• Hyponatremia and hypervolemia

Prevention and treatment

• Supportive care

• Fluid and sodium restriction

• Treat the hyperkalemia, acidosis

• Dialysis

Dialysis

• Increased intravascular volume leading to CHF, Pulmonary edema, intractable hypertension

• Non-responsive hyperkalemia

• Symptomatic uremia – lethargy, neurologic changes, seizures

Chronic Renal Failure

• Impaired homeostasis due to structural damage to kidney– Metabolic acidosis– Hypocalcemia– Hyperphosphatemia– Altered Vit D metabolism– Toxemia

Acute renal failure Chronic Renal failure

History recent drug administration, toxin exposure,surgery/hypovolemia

polyuria, polydipsia

Urine output oliguria polyuria

Kidney size normal to large small

Anemia absent present

Metabolic bone disease

absent present 

Etiology

• Diabetes Mellitus

• Hypertension

• Glomerulonephritis

• PKD

• Obstruction

• Infection

Stages

• Decreased renal reserve

• Renal insufficiency

• Renal failure

• Uremia

Stages

• Decreased renal reserve – GFR 50-75%– S. creatinine, BUN : normal

Stages

• Renal insufficiency – GFR < 50%– S. creatinine, BUN : start to rise– Mild anemia, hyposthenuria, nocturia– Increase in serum PTH– Azotemia/metabolic acidosis may occur

Stages

• Renal failure ( GFR 10-25%)– GFR < 10-25%– Marked anemia, severe acidosis– Hypocalcemia, hyperphosphatemia

                                                                                   

            

Stages

• Uremia– >90% nephron mass destroyed– S. creatinine, BUN : sharp rise– Severe symptoms

Pathogenesis

• Intact nephron hypothesis

• Trade off hypothesis

• Glomerular hyperfiltration hypothesis

Intact nephron hypothesis

• GFR is reduced, number of functional nephrons is reduced, but amount of solutes excreted remains same

• When >75% nephron mass is destroyed – BUN and S. creatinine begin to rise

Trade off hypothesis

• Increased blood conc. of some solutes stimulate secretion of other factors

• Retention of phosphate – release of PTH – increased Ca levels & reduced phosphate, reduced bicarbonate absorption – acidosis ,osteomalacia, calcification

Glomerular hyperfiltration hypothesis

• With progressive loss of some nephrons, hyperfiltration occurs in the remaining – leads to fibrosis and scarring

• Any added stress precipitates Uremia

Alterations of metabolism and function

• Disorders of Urine• Disorders of Water and Sodium balance• Disorders of Potassium balance• Metabolic Acidosis• Renal Azotemia• Renal Hypertension• Calcium, Phosphate and bone metabolism• Renal anemia and bleeding tendency

Disorders of Urine

• Initial nocturia, polyuria, later oliguria, anuria

• Isosthenuria – s.g. : 1.010, 285mOsm/L

• Urinary sediment contains cells and casts

Disorders of Water and Sodium balance

• Continued ingestion of salt – CHF, Hypertension, edema

• Excess water ingestion – Hyponatremia, hypervolemia, weight gain

• ECF depletion - shock

Disorders of Potassium balance

• Hyperkalemia if GFR < 5%

by potassium sparing diuretics and in Diabetes mellitus(hyporeninemic hypoaldosteronism)→reduced angiotensin II & impairs aldosterone secretion.

Metabolic Acidosis

• Metabolic acidosis

– Impaired ability to excrete H+

– Decreased NH4 + excretion

– Retention of phosphate

Renal Azotemia

• Increase of non-protein-nitrogen

• Urea, creatinine, phenols, amines, urates, guanidines

Renal Hypertension

• Fluid and Na overload(usual cause)

• Hyper-reninemia(less often) by failing kidney in response to falling renal perfusion.

Calcium, Phosphate and bone metabolism

• Diminished absorption of calcium from the gut

• Overproduction of parathormone

• Disordered Vit D metabolism

• Chronic metabolic acidosis

• Hypophospatemia

Renal anemia and bleeding tendency

• Lack of erythropoietin

• Bone marrow suppression

• Bone marrow fibrosis due to PTH

• Aluminum toxicity

• Dialysis related blood loss

• Coagulation defects – mainly platelet related

Uremia

• End stage of renal failure

Etiology & Pathogenesis

• Urea & other small m.w. molecules

• Middle molecules

• Polypeptide hormones

Urea & other small m.w. molecules

• When Blood urea > 300mg/dL – anorexia, weakness, headache, vomiting and bleeding

• Phenol, cresol, catechol, hydroquinone

• Methylguanidine

• Polyamines – putrescine, cadaverine, spermidine

Middle molecules

• Mol wt – 300 to 5000

• Greater morbidity

• In vitro – neurotoxicity, inhibits hemopoiesis, lymphoblast transformation, glucose utilization, fibroblast proliferation, leukocyte phagocytic activity and platelet aggregation

Polypeptide hormones

• Insulin, Glucagon, PTH, gastrin, calcitonin

• Trade off hypothesis

Alterations of metabolism and function

• Neuromuscular

• Cardiovascular and pulmonary

• Hematological

• Gastrointestinal

• Endocrine and metabolic

• Dermatologic

• Immunologic

Neuromuscular

• CNS – mild insomnia to seizures, coma

• PNS – restless legs syndrome, foot drop

• Aluminum toxicity, disequilibrium syndrome

Cardiovascular and pulmonary

• CHF, Pulmonary edema

• Uremic pericarditis

• Arrhythmias

• Accelerated atherosclerosis

Hematological

• Lack of erythropoietin

• Bone marrow suppression

• Bone marrow fibrosis due to PTH

• Aluminum toxicity

• Dialysis related blood loss

• Coagulation defects – mainly platelet related

Gastro intestinal

• Nausea, vomiting

• When GFR<10%, anorexia

• Uremic colitis, peptic ulcer

• Uremic gastroenteritis

Endocrine and metabolic

• Low estrogen in women – amenorrhoea, infertility

• Low testosterone in men – impotence, oligospermia, germ cell dysplasia

• Increased half life of insulin

Dermatologic

• Pallor due to anemia

• Gray discoloration due to hemochromatosis

• Ecchymosis & hematomas

• Pruritis & excoriations

• Uremic frost

Immunologic

• Immune suppression

Prevention & treatment

• Conservative

• Dialysis – Peritoneal / hemodialysis

• Renal transplantation

dialysate out dialysate in

Process of CAPD