Chronic Renal Failure

Chronic renal failure qiubo TEL:15153701881

chronic renal failure definition: -

a pathophysiologic process with multiple etiologies reduced of nephron number and function A state, in which there has been an irreversible loss of renal function, must depend upon dialysis or transplantation - “The world kidney day”, the second tuesday in March every year - Be a great social and economic burden on the whole world, in USA, the cost on therapy for chronic kidney disease has been rised to 20,000,000,000 dollars - Be the leading killer to mankinds health

definition 1.Azotemia - elevated blood urea nitrogen (BUN >28mg/dL) and creatinine (Cr>1.5mg/dL) 2.Uremia - azotemia with symptoms or signs of renal failure 3.End Stage Renal Disease (ESRD) - uremia requiring transplantation or dialysis 4.Chronic Renal Failure (CRF) - irreversible kidney dysfunction with azotemia >3 months 5.Creatinine Clearance (CCr) - the rate of filtration of creatinine by the kidney (GFR marker) 6.Glomerular Filtration Rate (GFR) - the total rate of filtration of blood by the kidney 7.Chronic kidney disease (CKD) from National Kidney foundation, K-DOQI, chronic kidney disease guidelines

difference Chronic renal failure? chronic kidney disease? Chronic kidney diseae including patients in stage 1, GFR is normal or elevated Aims: to appeal more attention to the kidney disease, prevent the patients develop renal failure quickly

Major Causes of CRF In china, glomerulonephritis, diabetic, hypertension,and polycystic renal disease are the leading underlying etiologies of CRD or ESRD But in the advanced countries, such as the USA, diabetic is the leading cause, and then hypertension, glomerulonephritis and polycytic kidney disease

Etiology 1.Primary glomerular diseases a.focal and segmental GN b.membranoproliferative GN c.IgA nephropathy d.membranous nephropathy

Etiology 2.Secondary glomerular diseases a.diabetic nephropathy b.Amyloidosis c.post-infectious GN d.HIV-associated nephropathy e.Collagen vascular disease f.Sickle cell nephropathy

Etiology 3.Tubulointerstitial nephritis a.Drug hypersensitivity b.heavy metals c.analgesic nephropathy d.Reflux/chronic pyelonephritis e.Idiopathic

Etiology 4.Hereditary diseases a.polycystic kidney disease b.medullary cystic disease c.Alports syndrome 5.Obstuctive nephropathies a.prostatic disease b.retroperitoneal fibrosis/tumor 6.Vascular diseases a.hypertensive nephrosclerosis b.renal artery stenosis

Common causes of Chronic Renal Failure Glomerulonephritis Diabetes Mellitus Hypertension Chronic pylonephritis/reflux Polycystic kidney disease Interstitial nephritis Obstruction Unknown 12%

25% 25% 10% 10% 10% 5% 3%

pathophysiology initiating mechanisms -- specific to undrelying etiology

progressive mechanisms --- non-specific compensatory hypertrophy of surviving nephrons – - adaptive hyperfiltration – –

- mediated by vasoactive molecules, cytokines, growth factors - increased glomerular capillary pressure and flow (hyperperfusion, hypertension, hyperfiltration)

– but, cannot last long – sclerosis of remaining nephrons

chronic renal failure diabetes damage to kidney

hypertension glomerulonephritis

loss of renal mass (nephrons) hypertrophy & hyperfiltration of remaining nephrons “hypertension” of remaining nephrons

glomerulosclerosis

Pathophysiology and biochemistry of uremia Presently, the main toxins responsible for uremic syndrome remain elusive Urea may contribute to some symptoms, including: anorexia, malaise, vomiting Additional categories of nitrogenous excretory products include urates, polyamines, etc. which molecular mass (500-12000 Da, so-called middle molecules) Polypeptide hormones, including parathyriod hormone(PTH), insulin, glucagon,and prolactin rise with renal failure, production of erythropoietin(EPO) and 1,25dihydroxycholecalciferol are reduced Resulting in anemia, malnutrition, impaired metabolism of carbohydrates, fats, and metabolic bone disease

Clinical manifestation of CRF Disturbance in every organ system Develop slowly and asymptomatic until renal failure is far-advanced Dialysis can reduce the severity of the disturbance but is not a panacea Some disturbance resulting from impaired renal function fail to respond fully.

Sodium and water homeostasis Disrupt glomerulotubular balance and promote sodium retention Excessive sodium ingestion Lead to cumulative positive Na+ balance and extracellular fluid volume expansion(ECFV) Patients with CRD also have impaired renal mechanisms for fluid conserving Na+ and H2O ， will be prone to volume depletion,impair residual renal fuction

Potassium homeostasis Hyperkalemia Cause: constipation augmented dietary intake protein catabolism hemolysis hemorrhage transfusion of stored RBC metabolic acidosis medication(beta-blockers, ACE inhibitors ARB, K+-sparing diuretics)

Metabolic acidosis Is commom in CRF or ESRD Cause: a.reduced ability to produce ammonia b.hyperkalemia further depresses ammonia excretion c.with tubulointerstitial disease In most patients, the acidosis is mild, severe acidosis may occur when the patient is challenged with an excessive endogenous or exogenous acid load or loses excessive alkali

Renal osteodystrophy Osteitis fibrosis high bone turnover and high PTH levels Osteomalacia and adynamic bone disease low bone turnover with low or normal PTH levels, excessive active vitamine D, which suppress production of parathyroid hormone Symptoms: bony pain and proximal muscle weakness, spontaneous bone fractures can occur that are slow to heal Calcification of soft tissue and blood vessels

signs of CRF/ESRD 1. osteodystrophy failing kidney function electrolyte imbalance secondary hyperparathyroidism “renal” osteodystrophy

also

↓ GFR

↓ 1α -hydroxylase activity

↓ phosphorus excretion hyperphosphatemia ↑ PTH production

↓ vit D activation ↓ Ca2+ intake in gastr ↓ Ca2+ & PO4 3- reabsorption in distal tubules

Secondary hyperparathyroidism

↑ osteoclast activity osteitis fibrosis cystica slow bone mineralization osteomalacia

renal osteodystropy

Cardiovascular abnormalities The leading cause of morbility and mortality in patients with CRD at all stages!

Ischemic cardiovascular disease

risk factors traditional hypertention hypervolemia dyslipidemia smoking alcohol age over-weight

CKD-related anemia hyperphosphatemia hyperparathyroidism microinflammation dialysis

Congestive heart failure Cause: a.myocardial ischemic disease b.left ventricular hypertrophy c.salt and water retention heart failure and pulmonary edema usually respond promptly to vigorous dialysis

Hypertention and left ventricular hypertrophy cause:(hypertenyion) a.volume overload is the major cause b.elevation level of serum renin cause:(LVF) a.is the most ominous risk fator for morbility and mortality in CRF b.prolonged hypertention c.fluid volume overload

Pericarditis a.Pericardial pain with respiratory b.Accompanied with a friction rub c.Electrocardiographic abnormalities include: PR-interval depression ST-segment elevation d.Detected by echocardiography e.Sometimes lead to cardiac tamponade

Hematologic abnormalities

Anemia Observed beginning at stage 3 CRD and universal at stage 4 Reasons: a.insufficient production of EPO b.iron and folate deficiency c.severe hyperparathyroidism d.inflammation e.aluminum toxicity f.shorten red cell survial

Neuromuscular abnormalities Cause: retained nitrogenous metabolities vt6

. and middle molecules as well as PTH contribute to Manifestations: mind disturbance sleep disturbance neuromuscular irritability: hiccups,cramps,chorea Peripheral neuropathy initially,sensory nerves are involved than motor

Endocrine metabolic disturbance a.Parathyroid function b.Blood glucose slightly elevated c.Plasma insulin slightly elevated d.Many hypoglycemic drugs require dose reduction e.Metformin are contraindicated when GFRdiminished by 25%-50% f.In women,estrogen levels are low, inability to carry pregnancies to term g.In men, impotence, testosterone are low,growth, sexual maturation is often impaired

Dermatology abnormalities a.Calciumphosphate deposition, secondary hyperparathyroidism, and deposition of pigmented metabolities or urochrome and urea itself. b.Pruritus c.Skin necrosis

Evaluation and management

History and physical examination a.history: hypertension, diabetes,systemic infection,inflammation, metabolic disease, exposure to drugs and toxins, and family history of renal disease b.questions: appetite, diet, nausea, vomiting, short of breath, edema, weight loss, muscule cramps, pruritus c.Physical examination:blood pressure, funduscopy, abdomen palpation, prostate size

Laboratory investigation a.Focus on a search for clues to an underlying disease process and its continued activity b.Immunologic tests for systemic lupus erythematosus and vasculitis c.Serum and urinary eletrophoresis to preclude paraproteinemia d.Tests for determine the stage and complication: creatinine, GFR, urea, eletrolytes, alkaline phosphatase to assess metabolic bone disease 24h urine collection for protein excretion

Imaging studies a.Ultrasound examination: kidney size, obstructive uropathy b.Symmetric small kidneys support diagnosis of CFR,and indicate irreversible c.Normal size usually suggests acute renal failure d.Asymmetric kidney size suggests unilateral developmental abnormality or chronic renovascular disease e.MRI and doppler sonography are useful in assess the renal arteries and veins

Renal biopsy a.Reserved for patients with normal kidney size,diagnosis cannot be made by invasive means,or when the possibility of a reversible underlying disease . b.contraindication:bilateral small kidneys, polycytic kidney disease, uncontroled hypertension, urinary or perinephric infection, bleeding diathesis, respiratory distress, and morbid obesity

Establishing the diagnosis and etiology of CRD a.To distinguish newly diagnosed CRD from acute renal failure b.Chronic metabolic bone disease with hyperphosphatemia, hypocalcemia, elevated PTH level,normocytic anemia, bilateral reduced kidney size, strongly support CRF c.In advanced stages of CRD, definitive etiology becomes less feasible and is also of less therapeutic significance

treatment

1.Specific treatement aimed at selected underlying etiology of CFR,such as lupus vasculitis,optimal time for such therapy can made the function of the kidney reversible 2.To find out superimposed acute processes that lead to an acute and reversible decline in GFR 3.Include volume depletion, uncontroled hypertension, nephrotoxin of medications,and so on 4.Slowing the progression of CRD, aimed to stabilize the GFR or reduce the annual rate of decline

Reversible causes of renal failure reversible factors

Infection obstruction EFVD hyperkalemia hypercalcemia nephrotoxic agents hypertension congestive heart failure

diagnostic clues

urine culture and sensitivity tests catheterization and renal ultrasound orthostatic blood pressure serum electrilytes examination serum electrilytes examination drug history blood pressure physical examination chest X-ray

Protein restriction 1.Aim:ameliorating the complications of uremia to slow the rate of decline of nephron injury. 2. Protein requirement of 0.6g/d.kg is recommended 3.Dietary protein should be higher in essential amino acids 4.Energy requirements in the rage of 35kcal/kg.d are recommended

Reducing intraglomerular hypertension and proteinuria 1.aim:to slow the progression of nephron injury by ameliorating intraglomerular hypertension and hypertrophy 2.Proteinuria is considered a risk factor for progressive nephron injury 3.ACEI inhibitors and (angiotensin receptor blockers(ARB) are effective to reduce proteinuria, second-line therapeutic approch is calcium channel blockers

Disorder of water, sodium, potassium, and acidosis 1.Restriction of dietary intake and use of loop diuretics 2.Attention : excessive use of diuretics cause hypovolemia, thus lead to further decline in GFR 3.hyperkalemia: avoid potassium-containing or retaining medications,and dietary restriction of potassium,potassium-binding resins can promote gastrointestinal potassium loss 4.Metabolic acidosis:serum bicarbonate level should be maintained at >21mmol/l, sodium bicarbonate and calcium bicarbonate should be given to the patients

Disorder of mineral metabolism 1.Dietary phosphorus restriction should be less than 1000mg/d 2.Oral phosphorus-binding agents such as calcium carbonate given in divided doses three or four times dialy with meals 3.Vitamin D should be given the patients with hyperparathyroidism 4.Since adynamic bone disease is often a consequence of overzealous treatment of hyperparathyroidism, PTH should not be <120pg/ml

Hypertension 1.Should be controled to 130/80-85mmHg 2.In CRD patients with diabetes or proteinuria >1.0g/d,further reduced to 125/75mmHg 3.Volume control with salt restriction and diuretics is the mainstay of therapy 4.Because of the vascular-renal protective benefit, ACE inhibitors and ARB are recommended firstly.

Cardiovascular disease 1.Hyperhomocysteinemia may repond to vitamin therapy 2.Hyperlipidemia: HMG-coA reductase inhibitor. simvastatin and lovastatin can be selected

Uremic pericarditis 1.Should be intensify the dialysis in those already on dialysis 2.Pericardiectomy should be considered only if more conservative measures fail Congestive heart failure 1.Salt and water intake should be control 2.Diuretics are of value, loop diuretics often used 3.Digoxin should be used with caution 4.ACEI and ARB are effective in hear failure,but serum creatinine and potassium should be checked within 5-14 days

Anemia 1.Recombinant human EPO 2.Before treatment of EPO, iron stores should be available. 3.Anemia resistant to recommended doses of EPO often suggest: inadequate dialysis, hyperparathyroidism aluminum toxicity, chronic blood loss malnutrition, chronic infection

Medication dose adjustment 1.Drugs that >70% excretion is by nonrenal route, adjustment should not be needed 2.Meperidine, metformin, and other drugs with a renal route of excretion 3.Many drugs have nephrotoxicity,such as NSAIDs,should be forbiden. 4.Drugs aggravate the tendency to hyperkalemia, and further reduce GFR should be used with caution.

Renal replacement therapy

1.When conservative management of ESRD is inadequate,hemodialysis, peritoneal dialysis,and kidney transplantation are needed 2.When GFR <10ml/min, require renal replacement therapy 3.Absolute indication: severe volume overload severe hyperkalemia and acidosis encephalopathy pericarditis symptomatic uremia

• b.

c. d. e.

f.

Procedure for Chronic Hemodialysis Blood is run through a semipermeable filter membrane bathed in dialysate Composition of the dialysate is altered to adjust electrolyte parameters Electrolytes and some toxins pass through filter By controlling flow rates (pressures), patient's intravascular volume can be reduced Most chronic hemodialysis patients receive 3 hours dialysis 3 days per week

Peritoneal dialysis 1.Place a peritoneal catheter that allow infusion of a dialysate solution into the abdominal cavity.which served as “artificial kidney” 2.Exchange dialysate 3.The most common complication is peritonitis Kidney transplantation With the advent of more potent and welltolerated immunosuppressive drugs,kidney transplantation offers the potential for nearly complete rehabilitation