Renal Failure

CHRONIC RENAL FAILURE Lecturer prof. Yu.R. Kovalev

1

Over 50% of cases of chronic renal failure are due to diabetes mellitus and hypertension. Glomerulonephritis, cystic diseases, and other urologic diseases account for another 20-25%, and nearly one-sixth of patients have unknown causes.

2

COMMON CAUSES 1. Primary glomerular diseases (glomerulonephritis, IgA nephropathy a.o.) 2. Secondary glomerular diseases (diabetic nephropathy, amyloidosis, collagen vascular diseases a.o.) 3. Tubulointerstitial nephritis (drug hypersensitivity, heavy metals a.o.) 4. Hereditary diseases (polycystic kidney disease a.o.) 5. Obstructive nephropathies (prostatic disease, nephrolithiasis, tumor, congenital) 6. Vascular diseases (hypertensive nephrosclerosis, renal artery stenosis) 3

PATHOGENESIS Chronic renal disease is rarely reversible and leads to progressive decline in renal function. This occurs even after an inciting event has been removed. Reduction in renal mass leads to hypertrophy of the remaining nephrons with hyperfiltration, and the glomerular filtration rate in these nephrons are transiently at supranormal levels. These adaptations place a burden on the remaining nephrons and lead to progressive glomerular sclerosis and interstitial fibrosis, suggesting that hyperfiltration may worsen renal function. 4

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 the appearance of a granulur contracted kidney. Renal function is maintained by the hypertrophied nephrons. Since the concentrating fund ion is impaired, adjustment of urine volume becomes defective and polyuria with urine of specific gravity around 1010 occurs. The blood pressure goes up progressively and this form of secondary hypertension exerts its deleterious influence 5 on the kidney, heart, and brain.

GLOMERULAR DYNAMICS Angiotensin II produced locally modulates intraglomerullar capillary pressure and GFR. Angiotensin II predominantly causes vasoconstriction of postglomerular arterioles, thereby increasing the glomerular hydraulic pressure and filtration fraction.

Effect of the renin-angiotensin system

6

CLINICAL FEATURES Organ System

Symptoms – Signs

General

Fatigue, weakness – Sallow-appearing, chronically ill

Skin

Pruritus, easy bruisability – Pallor, ecchymoses, excoriations, edema, xerosis

ENT

Metallic taste in mouth, epistaxis – Urinous breath

Eye

Pale conjunctiva

Pulmonary

Shortness of breath,– Rales, pleural effusion

Cardiovascular

Dyspnea on exertion, retrosternal pain on inspiration (pericarditis) – Hypertension, cardiomegaly, friction rub

Gastrointestinal Anorexia, nausea, vomiting, hiccup Genitourinary

Nocturia, – Isosthenuria

Neuromuscular Restless legs, numbness and cramps in legs Neurologic

Generalized irritability and inability to concentrate, – Stupor, tremor, myoclonus, peripheral neuropathy 7

Intercurrent factors precipitate the development of advanced renal failure •electrolyte imbalance, •infection, •cardiac failure, •trauma, •blood loss, •excessive protein intake, •alcoholic bouts, •use of nephrotoxic drugs 8

ADDITIONAL SIGNS Anemia (normochromic, normocytic), erythropoetin ↓ Sometimes iron deficient (bleeding) Renal osteodystrophy (calcium ↓, phosphorus ↑) Metabolic acidosis Hypertension (may be malignant) – salt and water retention Uremic encephalopthy Uremic coagulopathy (platelet disfunction) Accelerated rate of atherosclerosis (hyperlipidemia) 9

ESTABLISHING THE ETIOLOGY Of special importance in establishing the etiology of CRF are a history of hypertension; diabetes; systemic infectious, inflammatory, or metabolic diseases; exposure to drugs and toxins; and a family history of renal and urologic disease. Drugs of particular importance include analgesics (usage frequently underestimated or denied by the patient), NSAIDs, gold, penicillamine, antimicrobials, lithium, and ACE inhibitors. In evaluating the uremic syndrome, questions about appetite, diet, nausea, vomiting, hiccup, shortness of breath, edema, weight change, muscle cramps, bone pain, mental 10 acuity, and activities of daily living are helpful.

URINE EXAMINATION Urine volume is high (2—3 litres in 24 h). Mild proteinuria may be evident. The most remarkable feature is the fixed specific gravity around 1010 (isosthenuria) and an osmolality of 300 mOsm/kg water. The presence of broad casts in urine confirms the chronic nature of the illness. The estimation of urinary loss of sodium helps in identifying saltlosing states. 11

BLOOD EXAMINATION Blood urea, serum creatinine, serum uric acid, and inorganic phosphates are elevated. Potassium balance generally remains intact in chronic renal failure until the GFR is less than 10-20 mL/min. In terminal stage potassium level is increased. Calcium and bicarbonate levels are reduced.

12

IMAGING Ultrasonography of the abdomen help in revealing the small size of the kidneys. The findings of small echogenic kidneys bilaterally (< 8,5 cm) by ultrasonography supports a diagnosis of chronic renal failure, though normal or even large kidneys can be seen with chronic renal failure caused by adult polycystic kidney disease, diabetic nephropathy, HIV-associated nephropathy, multiple myeloma, amyloidosis, and obstructive uropathy. 13

DIAGNOSIS The diagnosis of renal failure is made by documenting elevations of the urea and serum creatinine concentrations. The urinanalysis shows isosthenuria if tubular concentrating and diluting ability are impaired. The urinary sediment can show broad waxy casts as a result of dilated, hypertrophic nephrons. 14

DIAGNOSIS Evidence of previously elevated urea and creatinine, abnormal prior urinalyses, and stable but abnormal serum creatinine on successive days is most consistent with a chronic process. The most classic constellation of laboratory and imaging findings that distinguishes progressive CRF from acute renal failure are bilaterally small (<8.5 cm) kidneys, anemia, hyperphosphatemia and hypocalcemia with elevated PTH levels, and a urinary sediment that is inactive or reveals proteinuria and broad casts. 15

POSSIBLY REVERSIBLE CAUSES Reversible Factors

Diagnostic Clues

Infection

Urine culture and sensitivity tests

Obstruction

Bladder catheterization, then renal ultrasound

Extracellular fluid volume depletion Orthostatic blood pressure and pulse: BP ↓ and pulse ↑ upon sitting up from a supine position Hypokalemia, hypercalcemia, and Serum electrolytes, calcium, hyperuricemia (usually >15mg/dL) phosphate, uric acid Nephrotoxic agents

Drug history

Pericarditis, congestive heart failure

Echocardiography, physical examination, chest x-ray

Hypertension

Blood pressure

16

KIDNEY BIOPSY It should be reserved for patients with nearnormal kidney size, in whom a clearcut diagnosis cannot be made by less invasive means, and when the possibility of a reversible underlying disease process remains tenable so that clarification of the underlying etiology may alter management. The extent of tubulointerstitial scarring on kidney biopsy generally provides the most reliable pathologic correlate indicating prognosis for continued deterioration toward ESRD. 17

DIETARY MANAGEMENTCONTROL OF

HYPERTENSION 1. Protein restriction —Protein intake should not exceed 1 g/kg/d, and if protein restriction proves to be beneficial, it should not exceed 0.6 g/kg/d. 2. Salt and water restriction - For the nondialysis patient approaching end-stage renal disease, 2 g/d of sodium. A daily intake of 1-2 L of fluid maintains water balance. 3. Potassium restriction - Restriction is needed once the GFR has fallen below 10-20 mL/min less than 6070 meq/d. 4. Phosphorus restriction 5. Magnesium restriction 18

INDICATIONS FOR DIALYSIS Renal replacement therapy should not be initiated when the patient is totally asymptomatic; however, dialysis and/or transplantation should be started sufficiently early to prevent serious complications of the uremic state. Clear indications for initiation of renal replacement therapy include pericarditis, progressive neuropathy attributable to uremia, encephalopathy, muscle irritability, anorexia and nausea that is not ameliorated by reasonable protein restriction, and fluid and electrolyte abnormalities that are refractory to conservative measures. Serum creatinine must be >700 µ mol/L (>8.0 mg/dL) and the creatinine clearance must 19 be <0.17 mL/s (<10 mL/min).

ARTERIOVENOUS FISTULA

20

INTRAVENOUS CANNULA IN THE WRONG PLACE

This patient is right-handed. Non work arm must kept for arterio-venous fistula and it must not made any i/v injection there. 21

PROGNOSIS Patients undergoing dialysis have an average life expectancy of 3-4 years. The most common cause of death is cardiac dysfunction (48%). Other causes include infection (15%), cerebrovascular disease (6%), and malignancy (4%). Diabetes, age, a low serum albumin, lower socioeconomic status, and inadequate dialysis are all significant predictors of mortality. 22

KIDNEY TRANSPLANTATION Up to one-half of all patients with end-stage renal disease are suitable for transplantation. Age is becoming less of a barrier. Two-thirds of kidney transplants come from cadaveric donors; the remainder from living related or unrelated donors. Immunosuppressive drugs include corticosteroids, azathioprine, cyclosporine a.o. A patient with a cadaveric renal transplant typically requires stronger immunosuppression than patients with living related kidney transplants. However, this depends to a great extent on the degree of HLA-type matching. 5-year survival rates 72% for living related and living unrelated donor transplants and 58% for cadaveric donor 23 transplants.