1. NEPHROLOGY FOR STEP 3 By James K. Rustad, M.D. Copyright © 2009 All Rights Reserved.

2. Outline  Renal Failure (Post-Renal, Pre-renal and Intra- renal)  Glomerulonephritis  Nephrotic syndrome  Acid-Base Disturbances  Imbalances of Sodium

3. Post-Renal  Distended bladder on exam.  Large volume diuresis after passing urinary catheter.  Bilateral hydronephrosis on ultrasound.  Post-void residual > 200 ml is suspicious.  Black arrow = renal capsule Black arrowhead = sinus fat White arrow = dilated calyx White arrowhead = renal cortex

4. Hydronephrosis  Large hypoechoic area (black on U/S = no echoes) in center of kidney. Dilation extends into the parenchyma. The normal hyperechoic area in the center of the kidney (hilum) is replaced by a large hydronephrotic renal pelvis. This kidney has hydronephrosis due to obstruction of upper ureter.

5. Treatment of Obstruction  Lower tract: Foley cath.  Upper tract: Ureteral stent or percutaneous nephrostomy.

6. Pre-renal  Hypotension.  Hypovolemia (decreased renal perfusion).  CHF: pump doesn’t work, can’t perfuse kidney.  Constrictive pericarditis: heart cannot fill, can’t perfuse kidney.  GI Bleed (digested blood is source of urea).  Excess diuresis.  Dehydrated patient may have high BUN (azotemia) due to lack of fluid volume to excrete waste products.  Nothing wrong with kidney itself – will try to absorb sodium to maintain volume.  Treat the underlying cause! Pre- renal usually improves with IVF

7. Pre-renal vs. Renal Pre-renalRenal BUN/Creatinine>20:1<20:1 Urine sodium< 10  20 FENa< 1> 1

8. Intra-Renal  Acute Tubular Necrosis (ATN)  Caused by hypoperfusion to the point of tubular cell death or from toxic injuries.  Muddy Brown Casts

9. ATN (continued)  Typically begins immediately after study. Renal function recovers after 3-5 days.  Prevent: Hydration, ½ NS 75 cc/hr 8-12 hr before and after study.  Acetylcysteine 600 mg BID for 2 days if diabetes, CHF, CRI.  Begins at least 5 days after treatment. Contrast NephropathyAminoglycoside Toxicity

10. Rhabdomyolysis leading to ARF  Labs: CPK elevated, Urine dipstick (urinalysis best initial test) shows blood but no RBC on microscopy.  Urine myoglobin most accurate.  Tx: IVF, IV sodium bicarbonate to alkalinize urine to solubilize myoglobin.  Mannitol and diuresis decrease contact time of myoglobin with tubule.

11. Clinical Situation  Patient is brought to the emergency room after a seizure leading to prolonged immobility on sidewalk. Next step?  A) Urinalysis  B) Urine Myoglobin  C) EKG  D) CPK  E) Phosphate level  F) Creatinine

12. Acute Rhabdomyolysis  EKG most urgent step.  Severe muscle necrosis leads to Hyperkalemia.  Look for peaked T waves. Treat with immediate IV calcium gluconate, insulin, glucose.  Order Potassium level (cellular destruction).  Order Calcium level (hypocalcemia): damaged muscle may bind increased calcium. Hyperphosphatemia may lead to calcium binding with phosphate.  Order chemistries to detect decreased serum bicarb.

13. Acute Interstitial Nephritis  The Pentad:  Acute Renal Failure  Fever  Rash  Arthralgia  Peripheral blood eosinophilia  Urine: WBC casts, eosinophil positive (Wright Stain)  Causes: Penicillin, Sulfonamide, Rifampin, Allopurinol, Indinavir, 5-aminosalicylates, Proton Pump inhibitors.  If NSAID induced: Fever, rash, eosinophilia, eosinophiluria usually absent.  Treatment: Stop medication! Prednisone may be prescribed.

14. Glomerulonephritis  RBC Casts, Dysmorphic RBC  Hematuria, proteinuria, HTN  Causes:  IgA Nephropathy  Post-streptococcal GN  Wegener’s granulomatosis  Goodpasture Syndrome  Endocarditis  Lupus Nephritis

15. IgA Nephropathy (Berger’s Disease)  History of URI 1-2 days before presentation + Painless recurrent hematuria  Recurrent hematuria following exertion  Serum IgA increased in 50% of patients  Normal complement  Renal Biopsy to confirm  Treatment: ACE inhibitor and ARB  Consider adding Fish Oil  Prednisone if tx-refractory or nephrotic syndrome/markedly proliferative disease.

16. IgA Nephropathy Biopsy: Mesangial Hypercellularity

17. IgA Nephropathy Immunofluorescence  IgA mesangial deposits = characteristic and defining feature of the disease  Deposits are exclusive of IgA in only ~26% of cases; usually accompanied by IgG (~37%) or IgM (~13%), and the three Igs may be present in ~25% of cases.  However, IgA must be dominant or codominant

18. Post-streptococcal GN  URI 7-10 days before presentation  “Cola or tea” colored urine  Periorbital edema/HTN  ASO titer, Low serum complement  Treat infection/HTN

19. Clinical Scenario  Patient with sinusitis, rhinorrhea, bloody nasal discharge and cough, shortness of breath, hemoptysis.  Hematuria, Proteinuria and Renal Failure.  + for c-ANCA  Most likely diagnosis?

20. Wegener’s granulomatosis  Confirm with biopsy of nasopharyngeal lesion if possible.  Alternative: renal biopsy (crescentic necrotizing GN). Focal or diffuse necrotizing extracapillary GN is histological hallmark of ANCA-associated Vasculitis.  Tx: Corticosteroid and Cyclophosphamide

21. Good Pasture Syndrome  Hemoptysis + Hematuria  Proteinuria + Renal Failure  Anti-GBM antibody!  Tx: Plasmapheresis + Prednisone + Cyclophosphamide

22. Lupus Nephritis  Type I: Minimal Mesangial  Type II: Mesangial Proliferative  Type III: Focal Proliferative  Type IV: Diffuse Proliferative  Type V: Membranous  Type VI: Advance Sclerosis

23. Nephrotic Syndrome  Not enough albumin (Hypoalbuminemia)  Edema  Proteinuria > 3.5 gm/24 hours  Hyperlipidemia

24. Nephrotic Syndrome  Renal causes: Minimal Change Disease, Membranous Nephropathy, FSGS  Systemic: SLE, Diabetes, Amyloidosis

25. Minimal Change Disease

26. Electron Microscopy Normal vs. MCD  Normal Kidney  MCD: The individual foot processes can no longer be made out- they have all just “melted” together into a single thin layer. Barrier in filtration process can no longer keep protein from being filtered out of the blood and into urine.

27. Membranous Nephropathy  Most common cause of Nephrotic syndrome in adults.  Causes: idiopathic, carcinoma, Hep B, Hep C, SLE, Drugs: Penicillamine, Captopril, Gold  Treatment: Prednisone

28. Kidney Biopsy Review  When all or at least more than 80% of the glomeruli seen in the biopsy is affected.  Only certain proportion of the glomeruli seen in the biopsy involved. DIFFUSEFOCAL

29. Kidney Biopsy Review  When the entire globe of the glomerulus is affected.  Only a segment of glomerulus involved. GLOBALSEGMENTAL

30. Focal Segmental Glomerular Sclerosis  Most common cause of Nephrotic syndrome in black patients, obese patients, IVDA, heroin abuse, HIV.

31. Acid-Base Disturbances

32. Normal pH  7.4 = 40 nmol/L  24 X 40/24  H + = 24 X PCO2 (respiratory)/HCO3- (metabolic)  pH < 7.4 is acidotic

33. Anion Gap  (Na+) – (Cl- +HCO3-)  MUDPILES  Methanol  Uremia  DKA  Paraldehyde/Propylene glycol  INH/Iron  Lactic acidosis  Ethylene glycol  Salicylates  “My name is MUD!”

34. Normal anion gap (8-12 mEq/L)  Diarrhea  Glue sniffing  Renal tubular acidosis  Hyperchloremia

35. Metabolic Acidosis: Compensation  For every 1 mEq HCO3- down, there is 1.3 mmHg PCO2 down  Increased ventilation, blow off CO2

36. Metabolic Alkalosis  Vomiting (urine chloride < 20)  Diuretic use (except carbonic anhydrase inhibitors): Ucl>20  Antacids/milk-alkali syndrome  Hyperaldosteronism  Bicarbonate addition  Loss of H+ from GI tract or kidney  Loss of Chloride from GI tract or kidney  Adaptation: 0.7 mm Hg of PCO2 up for every 1mEq/L up of HCO3-  Decrease ventilation!

37. Respiratory Acidosis  Primary disturbance?  PCO2 Up  Acute causes:  Airway obstruction  Status asthmaticus  Alveolar defects (pulmonary edema, pneumonia)  CNS depression, neuromuscular impairment  Ventilatory restriction (flail chest with rib fractures)  Chronic causes: COPD, abnormal chest wall mechanics.  Compensation: Acute (for any PCO2 up go 1-3 mEq/L up in HCO3-)  Chronic: For any 1 mm Hg up in PCO2 go up 0.4 mEq/L in HCO3-)

38. Respiratory Alkalosis  Primary disturbance?  PCO2 down  Cause:  High altitude residence  Pregnancy, Pulmonary disorder, CNS disease, Aspirin intoxification  Hepatic failure, Sepsis  Anxiety Hyperventilation

39. High Carbon Dioxide Respiratory AcidosisMetabolic Alkalosis CO2HighHigh (compensation) pH<7.4>7.4

40. Low Carbon Dioxide Respiratory AlkalosisMetabolic acidosis CO2LowLow (compensatory) pH>7.4<7.4

41. High Bicarbonate Metabolic AlkalosisRespiratory acidosis BicarbHighHigh (compensation) pH>7.4<7.4

42. Low Bicarbonate Metabolic acidosisRespiratory alkalosis BicarbLowLow (compensation) pH<7.4>7.4

43. Clinical Scenario: Aspirin Overdose  Causes two different primary disturbances: Respiratory Alkalosis and Metabolic Acidosis  Look for co-existing tinnitus, hypoglycemia, vomiting, history of “swallowing several pills.”  Alkalinize urine with Bicarbonate: speeds excretion.

44. Imbalances of Sodium

45. Hypernatremia  Serum Na+ > 145  Causes: Diabetes insipidus, dehydration.

46. Diabetes insipidus  Lab: Urine osmolality less than serum.  How do you differentiate between central and nephrogenic DI?  Vasopressin challenge:  Uosm increases in central, minimal change in nephrogenic.

47. Central vs. Nephrogenic DI  Central: Decreased production of vasopressin (trauma, neurosurgery, idiopathic). Treatment: intranasal DDAVP.  Nephrogenic: renal tubules unresponsive to vasopressin (Lithium, Demeclocycline, hypokalemia, hypercalcemia). Treat the cause, thiazide or amiloride.

48. Clinical Scenario  78 year old male from nursing home with altered mental status, serum sodium 160. BUN/Cr high and Uosm very high >800. Started DSW: after 10 hours the patient developed a seizure. What happened?  Rapid correction of hypernatremia. In hypernatremic patient: slow correction 0.5 mEq/L per hour by free water or D5W (no more than 12 mEq/L over first 24 hours). Check serum sodium every 2 hours!

49. Hyponatremia HypovolemiaIsovolemiaHypervolemia Diarrhea Vomiting Diuretics SIADH Hypothyroidism Cortisol insufficiency Polydipsia Beer Potomania CHF Nephrotic syndrome Cirrhosis

50. Hyponatremia  In True hyponatremia: Serum Osmolality should be low.  Hyponatremia with normal plasma osmolality: Pseudohyponatremia due to hyperlipidemia or hyperproteinemia.  Hyponatremia with elevated plasma osmolality: mannitol or hyperglycemia. For every 100 above 100 mg/dl of glucose > correct serum Na+ 1.6. Example: Plasma glucose 400 and Serum Na+ 130 > corrected will be 134.8

51. Treatment of Hyponatremia  Asymptomatic: increase serum sodium 0.5 mEq/L per hour (10-12 mEq/L per day).  Hypovolemia: Use Normal saline.  Hypervolemia, SIADH: FLUID RESTRICTION!  Symptomatic: Hypertonic saline, 1-2 mEq/L per hour first 3-4 hr then 0.5-1 mEq/L per hour. No more than 10-12 mEq/L per day in first 24 hours.

52. Rapid Correction of Hyponatremia  Central Pontine Myelinolysis or Osmotic Demyelination Syndrome (flaccid paralysis, dysarthria, dysphagia).

53. Thank you for your attention!