Nephrology

1. Nephrology

2. Creatinine Clearance Most widely used test to estimate glomerular filtration rate (GFR) Creatinine is derived from muscle creatine Cockcroft � Gault formula

3. Renovascular Hypertension (RVHT) Etiology Common: Renal artery atherosclerosis Less common: Fibromuscular disease Diagnosis Duplex ultrasonography MRA Renal artery angiogram with specialized testing Treatment Medications Renal vein angioplasty / stenting Controversial � best option

4. Proteinuria Normal protein excretion less than 100 mg/day Spot urine protein / creatinine ratio in mg/dl compares well with 24-hr urine collection 0.1 = 100 mg/day 1 = 1000 mg/day 3 = 3000 mg/day

5. Proteinuria (Cont�d) Normal amounts of protein may cause a positive reaction in concentrated urine False positive reactions Alkaline Urine Antiseptics False negative reaction Myeloma (since immunoglobuins or light chains may not be detected)

6. Proteinuria Etiology Overflow � myeloma Glomerular � glomerulonephritis Decreased reabsorption � tubulointerstitial disease Altered renal hemodynamics � fever, exercise, standing upright, seizures Treatment � depends on etiology

7. Hematuria > 3-5 RBC/hpf Dipstick positivity without microscopic presence of RBC may be secondary to: Myoglobin (Rhabdomyolysis) Free hemoglobin (hemolysis) Ascorbic acid Antiseptics (Betadine) Lysis of RBC secondary to dilute urine (< 1.006)

8. Etiology of Hematuria Menstruation Urologic neoplasms Renal cystic disease Coagulopathies Sickle cell disease Nephrolithiasis Need to r/o cancer in those > 40 yrs by imaging test (US or IVP and cystography)

9. Hematuria/Special Diagnosis Benign Familial Hematuria Onset during childhood Unexplained microscopic / gross hematuria Family history of hematuria Loin Pain Hematuria Syndrome Severe flank pain, progressive Patients in their 30�s Treatment � opioids, nephrectomy

10. Leukocyturia > 3-5 WBC/hpf If clean void, same in men and women Dipstick sensitivity - > 90% Etiology False positive (contaminants) UTI Tubulointerstitial disease Nephrolithiasis (irritation)

11. Renal Biopsy Used to diagnose glomerular diseases or unusual causes of acute kidney failure Complication 1/10 � gross hematuria 1/100 � blood transfusion 1/1000 � nephrectomy Usually not indicated when urinary protein < 1gm/day, normal GFR, no systemic disease

12. Nephrotic Syndrome Diagnosis Urinary albumin > 3-3.5 gm/24 hrs Hypoalbuminemia Edema Hyperlipidemia

13. Nephrotic Syndrome Etiology Primary Membranous (most common) Minimal change Focal segmental glomerulonephritis (most common in blacks) Secondary DM SLE Hepatitis B, C HIV NSAID drugs Multiple others

14. Nephrotic SyndromeTreatment Treatment of primary cause ACE Inhibitors ? proteinuria ? serum albumin ? lipids Low Salt Diet / Diuretics - ? edema STATINS / Diet - ? lipids

15. Acute Glomerulonephritis Usually decreased GFR, oliguria, HTN and urine sediment with erythrocytes and casts Proteinuria usually NOT nephrotic range

16. Acute Glomerulonephritis IgA Nephropathy Most common form worldwide Presentation Asymptomatic hematuria Episodic gross hematuria following URI Course � variable Treatment � supportive

17. Acute Glomerulonephritis Henoch-Sch�nlein Purpura Presentation: arthralgias, purpura, abdominal pain No proven therapy

18. Acute Glomerulonephritis Poststreptococcal Glomerulonephritis (PSGN) Latency period of 10-14 days after infection with nephritogenic Group A B-hemolytic streptococca Lab ASO, anti-DNAse, decreased CH50 and C3 Course � usually self-limited

19. Acute GlomerulonephritisDiseases Associated with Reduced Serum Complement Level Postinfectious SLE Cryoglobulinemia Idiopathic membranoproliferative GN

20. Acute Glomerulonephritis Diseases Associated with Normal Serum Complement Minimal change Focal segmental glomerulonephritis Membranous IgA Henoch-Sch�nlein Purpura Anti-glomerular basement membrane Pauci-immune

21. Acute Glomerulonephritis Rapidly Progressive Glomerulonephritis (RPGN) Anti-GBM antibody disease when associated with pulmonary hemorrhage � Goodpasture�s Syndrome Treatment: immunosuppressives and plasmaphersis

22. Acute GlomerulonephritisRapidly Progressive Glomerulonephritis (RPGN) (Cont�d) Pauci-immune P-ANCA � polyarteritis C-ANCA � Wegener�s granulomatosis Sinus and lower respiratory Sx Treatment: Cyclophosamide/steroids

23. Tubulointerstitial Nephritis Affects tubules and space between the tubules Diagnosis is usually made on clinical grounds and history Etiology Allergic interstitial nephritis � reversible form Analgesic nephropathy � 1%-10% of patients with ESRD - acetaminophen, NSAID Labs � metabolic acidosis Urine � bland urinary sediment

24. Polycystic Kidney Disorder (PKD) Autosomal Recessive (ARPKD) Usually lethal in neonatal period Autosomal Dominant (ADPKD) Common cause of kidney failure Frequency 1/000, all races Symptoms (flank pain, hematuria, renal stones, HTN, UTI) 50% develop renal failure < 70 yr Associated with cerebral aneurysm Age < 30: two renal cysts Age > 30: at least two cysts in each kidney

25. Medullary Sponge Kidney Doesn�t cause renal failure Associated with hematuria, hypercalciuria, nephrocalcinosis Diagnosis by IVP showing small cystic outpouchings of renal papillary duct Treatment - supportive

26. Acute Renal Failure (ARF) / Acute Kidney Failure (AKF) Sudden diminution of GFR 2-5% of hospital admissions 30% of ICU patients 3 main etiologies Prerenal Renal � intrinsic Postrenal � obstructive

27. Prerenal Most common cause � ECF volume depletion ? intake, diarrhea, vomiting, hemorrhage, sepsis, third spacing, medications, NSAID, ACE, CHF, ascites

28. FENa = Urine Na/Plasma Na Urine Creat/Plasma Creat Useful marker for prerenal azotemia Usually < 1% Diuretics/osmotic diuresis � interfere with test Prerenal (Cont�d)

29. Patients with volume overload (CHF, ascites) have the same presentation (FENa, UA results) as those with prerenal azotemia ACE Inhibitors decrease resistance of glomerular efferent arterioles. This is associated with renal insufficiency in those with renal vascular disease, solitary kidneys or bilateral renal artery stenosis. Presents like prerenal. Usually reversible after discontinuation of the drug

30. Postrenal Azotemia Ultrasound evaluation appropriate tool Catheterization may identify post bladder obstruction (most commonly � prostate) FENa, Bun/Creat ratio are not reliable Postobstructive diuresis � usually physiologic because of Na and water retention and abnormal but transient abnormal renal tubule function Limited recovery if high-grade obstruction > 3 months

31. Acute Tubular Necrosis (ATN) Common in ICU patients Associated with renal ischemia/toxicity Onset insidious or acute Typically have initial oliguric phase followed by a diuretic phase (caused by renal tubular dysfunction) UA � pigmented/granular casts FENa � usually high � decreased urinary creatinine concentration

32. Acute Tubular Necrosis (ATN) Treatment Minimize further damage Correct volume status Use of diuretics � questionable efficacy Dialysis may �bridge� till spontaneous resolution in oliguric patients Mortality related to: age; preexisting chronic illnesses Infusion of dopamine � no data for clinical improvement

33. Contrast � Mediated Nephropathy Creatinine increases 1-2 days after exposure and peaks at day 3-5 Usually transient � resolves by 2 weeks Usually not associated with oliguria UA � non diagnostic FENa � low

34. Contrast � Mediated Nephropathy (Cont�d) More common in diabetes, older patients Best prevented � choose alternative diagnostic testing, avoid nephrotoxins, ensure optimal fluid balance, use of nonionic, less hyperosmolar agents (metrizamole) Use D5 � NS or � NS with acetylcysteine (p.o.) in high risk patients

35. Antibiotic � Induced Nephrotoxicity Insidious onset 1-2 weeks Most common drugs � amnioglycosides Other drugs � amphotericin B > 2 gms vancomycin

36. Antibiotic � Induced Nephrotoxicity (Cont�d) Common risk factors: Advanced age Volume depletion Renal insufficiency Prolonged duration of drug use Multiple nephrotoxic drugs FENa � high

37. Antibiotic � Induced Nephrotoxicity Aminoglycosides Potassium, magnesium wasting Associated with hypocalcemia Avoid excessive peaks (> 10 ?g/ml) and troughs (> 2 ?g/ml) (Gentamicin and Tobramycin) Once daily dose may be beneficial in prevention

38. Drug-Induced Acute Interstitial Nephritis Associated drugs � penicillins, quinolones, NSAID, diuretics, cimetidine, cephalosporins Diagnosis suggested by: Systemic hypersensitivity � fever, rash, eosinophilia; UA � sterile pyuria, eosinophiluria

39. Drug-Induced Acute Interstitial Nephritis (Cont�d) Eosinophiluria Special stains: Wright�s / Hansel�s Nonspecific � Acute prostatis, RPGN, cholesterol emboli Treatment: supportive

40. Acute Oliguric Urate Nephropathy Most common with lymphoproliferative and hematologic disorders and tumor lysis syndrome Preventive therapy Allopurinol before chemotherapy / radiation Volume repletion Urine pH > 6.5 using sodium bicarbonate

41. Hepatorenal Syndrome Thought to be a physiologic response to systemic complications of liver disease Most common in decompensated cirrhotics but may occur with fulminant hepatitis or hepatic malignancy

42. Hepatorenal Syndrome (Cont�d) Diagnosis Exclude other etiologies (ATN, interstitial nephritis, prerenal azotemia) Urine Na < 10 mEq / L (exclusion of diuretics) FENA < 1% Treatment � supportive Liver transplant

43. Rhabdomyolysis Etiology � muscle trauma, strenuous exercise, influenza, drugs, alcoholism, cocaine Associated with high CPK, creatinine levels, and rapid increases in creatinine of ? 2 mg / dl per day UA � dipstick ? heme Absent RBC on micro, pigmented cast

44. Rhabdomyolysis (Cont�d) Treatment Volume repletion Alkalinize the urine Furosemide if oliguria Prognosis � good

45. Renal Atheroemboli Rarely occur spontaneously - usually follows vascular interventions Diagnosis confirmed (if needed) by biopsy of muscle, skin or kidney that shows typical biconcave clefts in small vessels

46. Renal Atheroemboli (Cont�d) No treatment shown to be beneficial � Recovery of renal function poor Elevated sed rate hypocomplementia, leukocytosis, eosinophilia, eosinophiluria

47. Causes of End-Stage Kidney Disease Diabetes����������.40% Hypertension������.��27% Chronic Glomerulonephitis��..13% Cystic Kidney Disease����.3-4% Interstitial Nephritis������..4% Other (Obstructive, Lupus, HIV)����12%

48. Referral to a Nephrologist Consultant Recent NIH conference Female > 1.5 creatinine Male > 2.0 creatinine Confirm diagnosis / treatment

49. Important intervention to slow the progression Target BP < 130/80 for all renal disease/diabetics Target BP < 125/75 for proteinuria disease ( > 1 gm / 24 hr) ACE inhibitor best studied Hypertension Management

50. Diet Dietary Protein Restriction Remains controversial 0.6 mg to 1 gm / kg / d Renal Failure Diet 2 gm potassium 2 gm sodium

51. Anemia Management Anemia Usually due to deficiency of erythropoietin Normocytic, normochronic Treatment with recombinant erythropoietin goal Hct 33-36%

52. Anemia Management (Cont�d) ERYTHROPOIETIN Side effects HTN, headaches, flu-like illness No data on mortality reduction May improve morbidity and left ventricular hypertrophy

53. Renal Bone Disease Three main types Osteitis Fibrosa Due to secondary hyperparathyroidsim Subperiosteal bone resoiption of phalanges, distal clavicles, skull Bone turnover increased Lab ? PO4 ,?Ca, ? VitD 1.25 ? ? PTH Osteomalacia Bone tunover reduced Unmineralization bone (osteoid) 2nd to aluminum deposition Appears as osteopenia on X-rays Less common 2� to decrease use of aluminum antacids Adynamic bone disease Possible cause excessive suppression of PTH by calcitriol therapy

54. Renal Bone Disease (Cont�d) Symptoms Bone pain Fractures Treatment ? PO4 ? Ca to normal range, calcitriol

55. Uremia Clinical signs and symptoms related to renal disease consisting of fatigue, sleep disturbances, loss of appetite, nausea, vomiting, restless leg syndrome, asterixis, seizures Usually when GFR < 10 ml / min

56. Indications for Renal Replacement Hyperkalemia CHF Refractory metabolic acidosis Uremic symptoms GFR < 10 ml/min � nondiabetics < 15 ml/min - diabetics

57. Dialysis Home peritoneal dialysis Maximum control by patient Peritoneal catheter placement 2-4 week prior Gram positive peritonitis averages 1 episode / 18 mo Hemodialysis Requires AV fistula or graft weeks to months prior Central catheter for acute, urgent use Treatment of anemia, bone disease, hypertension still needed Overall survival: 78% - 1 yr, 40% - 5 yr

58. Renal Transplantation Overall survival: 95% 1 yr, 88% - 5 yr Clear survival advantage over dialysis Long waiting list therefore earlier referral wise Contraindications - Active infection, malignancy, dementia, significant medical disease, substance abuse Morbidity � acute rejection, complications of immunosuppressants

59. Nephrolithiasis 1-5% of population Men 2x the risk as women Presentation � colicky flank pain, microscopic / gross hematoma Diagnosis � ultrasound, IVP, Spiral CT Types of Stones Ca oxalate / phosphate 75% Uric Acid 10-15% Struvite 10-15% Cystine < 1%

60. Nephrolithiasis Calcium Stones Radiopaque Hypercalciuria usually present > 300 mg � male > 250 mg � female Causes Idiopathic hypercalciuria Hyperuricosuria Hyperparathyroidism Low urine citrate

61. Nephrolithiasis Calcium Stones (Cont�d) Treatment Ca restriction � not appropriate Low Na / 50 gm protein diet Avoid loop diuretics High fluid intake (clear urine) Thiazide diuretics

62. NephrolithiasisStruvite Stones Composed of magnesium, ammonium phosphate Causes by urease-producing bacteria Treatment: eradicate infection, remove stones

63. Etiology Hyperuricosuria Low urine pH Radiolucent Treatment � high fluid intake, allopurinol, urine alkalinization Nephrolithiasis Uric Acid Stones

64. Workup and Management of Nephrolithiasis Mostly calcium, < 5 mm Most will spontaneously pass 1st stone evaluation FMH, P.E., Lab � Chemistry panel, PTH, UA, Imaging � IVP,US, Spiral CT Stone analysis not usually warranted

65. Workup and Management of Nephrolithiasis (Cont�d) 1st stone treatment High fluid intake Pain control Recurrence 30% - 2 yr 50% - 5 yr Recurrent stone evaluation 24 hr urine � Na, Ca, oxalate, urate, citrate