1. Introduction to Renal Failure and Acute Renal Failure
Jeffrey T. Reisert, DO
University of New England
Physician Assistant Program
20-27 JAN 20010

2. Contact Information
Jeffrey T. Reisert, DO
103 Boulder Point Rd., Suite 3
Plymouth, NH
(fax)

3. Genitourinary Section-Part 1
Male urogenital disorders/Impotence
Nephrolithiasis
Urinary Tract Infections

4. Genitourinary Section-Part 2
Introduction to Renal Failure
Acute Renal Failure
Chronic Renal Failure
Glomerulopathies (builds on prior topics)
Tubular disorders (builds on prior topics)
Hematuria
Proteinuria

5. Introduction Two syndromes of renal failure Diagnosis-2 Patterns Acute
Chronic
Diagnosis-2 Patterns
Clinical suspect with signs and symptoms
Found incidentally on lab screen (serum or urine)

6. Agenda General evaluation of renal failure Definitions
Acute Renal Failure (ARF)
Etiology
Diagnosis/Evaluation
Treatment
Chronic Renal Failure (CRF)
Pathogenesis
Complications
Treatment of the complications

7. Definition-Renal failure
Spectrum of disease with declining kidney function
Decreased glomerular filtration rate
Resultant increase in nitrogenous waste products in the blood (azotemia)
Alteration in fluid an electrolytes
3. Carbs and fats turn into water and CO2 – easy to metabolize
Proteins turn into nitrogenous waste – what gives us problems – get build up.

8. Definitions-Part II
Oliguria=Urine output (UOP) of less than 400 or 500 cc/24 hours
Anuria=No UOP
Uremia
Decreased renal function
Azotemia
Symptoms
2. Need to R/O obstruction
3. Need all 3 of them

9. Definitions-Part III Polyuria Hematuria-blood in urine
Excessive or frequent urination
Excessive water intake
Medical conditions?
Diabetes insipidus (Inability to concentrate urine)
Renal disease
Hematuria-blood in urine
Proteinuria-protein in urine

10. Assessment
Labs
Urine
Serum
Radiographic

11. Assessment-Labs I Blood urea nitrogen-BUN Creatinine
BUN/Creatinine ratio
>40 in prerenal azotemia
<20 in intrinsic renal failure
Electrolytes
Potassium especially!
4. can’t excrete K you die

12. Creatinine
Goes up quickly in ARF due to ischemia and radio contrast (complication of x-ray dye studies such as IVP, CT scans)
Peaks 3-5d after contrast
Peaks 7-10d after ischemia
Not correlative with symptoms

13. Electrolytes Sodium reflects volume status
Potassium, phosphate, and uric acid increase

14. Assessment-Labs II Urine output (UOP)-Monitor I’s and O’s
Urine sodium (reflects concentrating ability of kidneys)
Body weight
Toxin levels (i.e.: CPK-MM fraction in rhabdomyolysis)
4. Need to dilute toxins.

15. Glomerular filtration rate
Collectively, the measure of renal function
If low, leads to azotemia
Can be estimated by serum creatinine
Affected by age, sex, weight, fluid status, and medical condition (illnesses, nutritional status, drugs on board, etc.)
Creatinine used as a surrogate marker as levels vary little day-to-day.
Creatinine is secreted in the proximal tubule

16. Assessment-Labs III Creatinine clearance ml/min/1.73 per square meter
Reflects the glomerular filtration rate
Normal
Lower in premies
Measured or Calculated methods (next slides)

17. Creatinine Clearance [(Urine volume (ml/min) x Urine Creatinine)
Divided by Serum Creatinine] x
1.73/Body Surface Area
-Involves 24 hour urine test mated with serum creatinine
-Fairly accurate and easy
-Once a year?
Can be measured accurately by inulin (Usually in research)…..Is filtered but not reabsorbed or secreted in the renal tubules.
Also by radionuclide markers such as I125 iothalamate or EDTA (uncommon use) because……

18. Creatinine Clearance Estimates
Cockcroft-Gault equation
Men:(140-age) x (wt in kg) divided by 72 x serum creatine
For women multiply by 85% to account for smaller muscle mass (0.85 of men’s estimate)
Use in hospitals with IV antibiotic dosing

19. Assessment-Labs III Fractional excretion of Na+
(Urinary Na+ x Plasma Creatinine x 100%) divided by (Plasma Na+ x Urinary Creatinine)
Not done as often

20. Azotemia Defined as excess of urea and nitrogenous compounds in blood
Due to breakdown of protein
(Metabolism of carbohydrates and fats yields water and CO2)
If symptoms, use term “uremia”

21. Assessment-Radiographic
Ultrasound
Excludes obstruction
?Small kidneys--->CRF
Advantages
Non invasive
No risky contrast dye
Readily available
2. Most common treatable form of RF
Great way to screen for RF – esp if you think obstructive

22. Assessment-Radiographic II
Plain x-Ray
Flat plate (?stone)
Pyelogram-Inject a dye, cleared through kidney
Retrograde pyelogram-Inject dye inside urinary collection system (intravesicular, using cystoscope) CT
Probably better but dye risk in face of rising creatinine
MRI

23. Assessment-Wrap up Avoid contrast in ARF or CRF not on dialysis
Biopsy may be needed in ARF for intrinsic disease
Ultrasound is easy and helpful

24. Complications of ARF Volume overload Hyponatremia Hypocalcemia
Decreased sodium and water excretion
Resultant weight gain, heart failure, and edema
Hyponatremia
Hypocalcemia
Paresthesias, cramps, seizures, confusion
Build up of waste causes neurologic problems

25. Complications of ARF II
Hyperkalemia, phosphatemia, magnesemia
Potassium increases 0.5mmol/l/d in uremia
Treat hyperphosphatemia with calcium or aluminum
Metabolic acidosis
Hypertension (Moreso in CRF)

26. General treatment of ARF
Prevention!!! (Avoid nephrotoxins, diabetes control, etc.)
Reverse poisons (ETOH in ethylene glycol, bicarbonate in acidosis)
Restore fluid volume and electrolyte balance (Saline/crystalloids, colloids, blood)
Dialysis when needed (Acute if responsive (i.e.: dialyzable toxin) or in CRF)
Relieve obstruction (Easiest way to fix ARF!)

27. Acute renal failure
Definitions
Classifications/Types
Treatment

28. Defined Renal failure of recent onset (hours to days to weeks)
Typically little symptoms
Can be found on random lab test or when suspect
If acute obstruction, symptoms (below)

29. Classification Prerenal renal failure (Renal hypoperfusion)-55%
Renal/Parenchymal/Intrinsic-45%
Post renal (Obstructive)-5%
dehydration, HF, Shock, anything that lowers perfusion. in
Most treatable, most uncommon

30. Outcome Usually reversible Can recover even if almost no function
Nephrology opinion?
If it gets fixed it gets better, if not then you get chronic renal failure

31. Prerenal azotemia Due to renal hypoperfusion
Usually reversible if restoring renal blood flow (RBF)
Parenchyma usually not damaged
In severe cases, ischemia/injury
Sluggish kidneys

32. Etiology Hypovolemia Renal hypoperfusion Fluid loss
Decreased cardiac output
Decreased systemic vascular resistance
Renal hypoperfusion
See next slides
1. Shock – intravascularly dehydrated

33. Fluid or blood loss Dehydration GI bleeds Burns
Osmotic diuresis (i.e.: diabetes)
Sequestration (i.e.: pancreatitis)
5. Fluid puddles where it’s not supposed to be.

34. Decreased Cardiac Output
Acute MI
CHF (perhaps most common among hospital patients)
Arrhythmias
Pulmonary embolism (PE)
Mechanical ventilator

35. Altered systemic vascular resistance
Sepsis, antihypertensives, anesthetics, anaphylaxis

36. Hypovolemia
Leads to epinephrine release and subsequent vasoconstriction
Also activations of renin angiotensin system-->Vasoconstriction
Release of arginine vasopressin (AVP)

37. Renal hypoperfusion Renal vasoconstriction due to epinephrine
ACE inhibitors
Cyclooxygenase inhibitors (i.e.: NSAID’s)-Also lead to volume depletion
Hyperviscosity syndromes

38. Hepatorenal syndrome Cirrhosis leads to intrarenal vasoconstriction
Sodium retention
Precipitated by bleeding, paracentesis, diuretics, vasodilation, cyclooxygenase inhibitors
Tx supportively and “pray”

39. Prerenal azotemia-Assessment
Symptoms
Thirst, dizzy
Signs
Low blood pressure, tachycardia, orthostasis
Low UOP
Have to monitor. Usually in ICU pt’s – just water and watch

40. Lab evaluation Urine volume Urine microscopy
Hyaline/bland casts due to concentrated urine

41. Intrinsic renal failure
Renovascular obstruction-Large vessel disease
Glomerular or microvascular diseases

42. Renovascular obstruction
Obstructed renal artery (Atherosclerosis, thrombus)
Renal vein obstruction (Thrombosis, external compression)
Causes damage to kidneys at cellular level

43. Glomerular diseases Glomerulonephritis Vasculitis
Acute tubular necrosis
Ischemic or nephrotoxic
Interstitial nephritis
Renal allograft rejection
Will expand in later section

44. Vasculitis Kidneys are one of several very vascular organs
Hemolytic uremic syndrome
Thrombotic thrombocytopenic purpura
Disseminated intravascular coagulation
Toxemia
Accelerated HTN
Lupus
?Include sickle cell disease
3. Jam up blood vessels with clots.

45. Acute tubular necrosis
Most susceptible area of the nephron to ischemia is the renal tubule
Ischemia from prerenal azotemia (Most common)
Prerenal azotemia is the most common cause of intrinsic renal failure
Toxin induced
Often see casts (covered later)
Kidney ds caused by prerenal azotemia

46. Ischemia Hypoperfusion Resultant injury or ischemia Cortical necrosis
Either recover (tubules regenerate) or develop irreversible failure
4. Need dialysis

47. Nephrotoxins Radiocontrast (Intrarenal vasoconstriction)
Aminoglycosides (Decrease GFR)
Cyclosporin
Chemotherapy (Cisplatin)
Solvents (ethylene glycol)
Others
Commonly cause this (ATN).
1. Kidney becomes ischemic

48. Endogenous nephrotoxins
Rhabdomyolysis (Due to crush, injury, ETOH)
Hemolysis (toxic to renal tubule)
Uric acid (Same thing that causes gout)
Myeloma (Plasma cell malignancy)
Hypercalcemia (Causes renal vasoconstriction)
All like glue – kidneys get jammed up and don’t work

49. Interstitial Nephritis
Allergic (Antibiotics such as beta-lactams), NSAID’s, diuretics
Infection (Bacterial-pyelonephritis, viral-CMV, Fungus-Candidiasis)
Infiltration (Lymphoma, leukemia, sarcoidosis)
Idiopathic
Inflammation of kidneys

50. Intrinsic renal failure
Symptoms-Often none
May have history of nephrotoxin exposure
Signs-Azotemia on lab testing
Nephritic syndrome (Oliguria, edema, HTN, Urine sediment)
This suggests a glomerulonephritis or vasculitis
4. Inflammation of kidney – have the quadrad of sx listed above.

51. Intrinsic renal failure-Lab evaluation
Microscopy
Muddy brown casts (ischemia and nephrotoxic)
Red cell casts (acute glomerular injury or nephritis)
White cell casts (interstitial nephritis)
Eosinophilic casts (allergic nephritis)
Often no casts
Hematuria
First thing do UA,
Then use US to assess fxn. Help see if obstruction.

52. Intrinsic renal failure-Lab evaluation
Proteinuria due to impaired reabsorption at the proximal tubules
Guided by etiology (i.e.: sedimentation rate if vasculitis)

53. Intrinsic renal failure-Treatment
Treat cause
Remove insult
Support, hope, and pray

54. Examples
Glucocorticoids in vasculitis and allergic interstitial nephritis)
Control blood pressure

55. Postrenal renal failure
Urinary outflow obstruction
Single kidney or urethral obstruction-->Anuria

56. Etiologies of postrenal azotemia
Prostate disease
Neurogenic bladder
I.e.: spinal cord injuries
Anticholinergics
Blood clots
Stones
Tumor or other extrarenal obstruction

57. Postrenal signs and symptoms
Bladder distension
Abdominal pain-colic
Renal distension (ultrasound)
History of risk factors (prostate disease, stones, etc.)

58. Treatment of obstruction
Urologist
Fix plumbing
May need nephrostomy tube or suprapubic catheter placed

59. Miscellaneous treatment wrap-up
Loop diuretics may restore diuresis
Dopamine may promote sodium and water excretion
Dialysis when needed
1. Just may need a jump start.

60. Wrap-up II--Dialysis Use
?BUN > 100
Uremia
Hypervolemia
Hyperkalemia
Acidosis
Toxins
Multiple
Include digoxin, others

61. More…… …to come in next slide set ARF – see if they have obstructed
See if they are underhydrated
If it’s intrinsic, needs more work.