Nephrology Review Leanna Tyshler, MD Chronic Kidney Disease Medical Advisor Transplant Liaison Syndromes of Renal Diseases • • • • • • Acute Kidney Injury Nephritic syndrome Nephrotic syndrome Asymptomatic proteinuria Chronic Kidney Disease/ESRD Asymptomatic hematuria • • • • • • Urinary tract infection Nephrolithiasis Tumors Electrolyte disturbances Acid-Base problems Hypertension Acute Kidney Injury • Rapid deterioration of renal function (48 hrs) >0.3 mg/dl ↑ of Cr or >50% ↑ of Cr UO < 0.5 mg/kg/h for 6 hrs • Syndrome – common (20% all ICU patients) – – – – High mortality/morbidity (about 50%) Multifactorial Non specific clinical symptoms Decreased UO • Oliguria: <400 ml of urine in 24 hrs • Anuria: <100 ml of urine in 24 hrs • Remember: 65% of patients are non-oliguric – Abnormal labs • Elevated BUN and Cr, “Azotemia” – accumulation of nitrogenous wastes • Acid-base, electrolytes disturbance, fluid balance Acute Kidney Injury Pre-Renal Renal Post-Renal Pre-Renal AKI – Decreased Renal Blood Flow • Intravascular Volume Depletion Blood loss GI losses: vomiting, diarrhea, ↓ po intake Skin losses: burns, sweat Renal losses: DKA, DI, Addison’s, Na wasting, diuretics • Decreased Effective Circulatory Volume Decreased CO: CHF, PE, Tamponade Hypotension: sepsis, shock, anaphylaxis, medication Third Spacing: bowel obstruction, hepatorenal, nephrotic, surgery Drug-induced: NSAIDs, CsA, FK506, ACEIs, ARBs Vascular: renal artery compromise, AAA, atheroemboli, vasculitis Acute Kidney Injury Pre-Renal Renal Post-Renal Causes of Obstructive Uropathy A 75 y.o. man c/o not feeling well, abdominal distension, and decreased urine. He was recently started on amitriptyline for insomnia. His creatinine is 5.1 (Cr 1.5 four months ago). A 75 y.o. man c/o not feeling well, abdominal distension, and decreased urine. He was recently started on amitriptyline for insomnia. His creatinine is 5.1 (Cr 1.5 four months ago). 1. What is the problem? 2. What do we need to do? Bladder Outlet Obstruction • Causes – BPH – Neurological disease – Drugs • Anticholinergic meds • Pain meds • Foley catheter insertion/renal US– diagnostic • Post-obstructive diuresis Acute Kidney Injury Pre Renal Vascular Renal Glomerular Post Renal Tubular Ischemia Toxins Pigments Interstitial 20 y.o. IDU with Endocarditis, Cr 3.7 Meds: Nafcillin, Gentamicin, Methadone, Ibuprofen UA: 1+ protein, uNa 70. What is the dx? What is the next step? What is the diagnosis? a) Acute Tubular Necrosis (ATN) b) Acute Glomerulonephritis c) Acute Interstitial Nephritis (AIN) d) Nephrotic Syndrome 20 y.o. IDU with Endocarditis, Cr 3.7 Meds: Nafcillin, Gentamicin, Methadone, Ibuprofen UA: 1+ protein, uNa 70 ATN due to Aminoglycosides - Common - Related to trough levels & duration; QD dosing ↓ toxicity; tissue half-life > serum half-life - Risk factors • Age, CKD, DM, volume depletion or hypoperfusion, other toxic drugs Contrast Nephropathy • Renal vasoconstriction/hypoxia, iodine- toxic • Risk Factors – CRI, DM, hypovolemia • 12-24 hrs post exposure, peaks in 3-5 days • Non-oliguric, FeNa <1% • Treatment/Prevention – NS 1-1.5cc/kg/hr 12 hours pre/post – Mucomyst (N-acetylcysteine), 600 mg BID pre/post – Bicarbonate A 66 y.o. man admitted with cellulitis, started on Cefazolin. On hospital day 5, the pt’s Cr 2.7 (Cr 1.1 two months ago) Other Labs: UA: 2+ WBCs, uNa=50, FeNa=1.5 What is your diagnosis? Acute Interstitial Nephritis What is the next step? - Often drug induced NSAIDS, rifampin, abx - 3-7 days after exposure - Fever, rash, eosinophilia, AKI - U/A: WBC, WBC casts + Hansel stain - Tx: can resolve spontaneously, steroids Acute Kidney Injury Pre Renal Vascular Renal Glomerular Post Renal Tubular Ischemia Toxins Interstitial GFR  Renin Angiotensin Blood Pressure JGA Normal Kidney Glomerular Diseases Primary Glomerulonephritis Secondary Systemic Diseases • • • • • • • • • • • • • • • • Acute Diffuse Proliferative GN Rapidly Progressive GN Membranoproliferative GN IgA Nephropathy Minimal Change Disease Membranous GN FSGS Chronic GN Hereditary Disorders • Alport’s syndrome • Fabry’s disease Systemic Lupus Erythematosus Diabetes Mellitus Amyloidosis Goodpasture’s Syndrome Polyarteritis Nodosa Wagener’s granulomatosis Henoch-Schonlein Purpura Bacterial Endocarditis Nephritic • • • • • • Hematuria Proteinuria Hypoalbuminemia GFR↓, Cr↑, BUN↑, Oliguria Edema (salt/water retention) Hypertension Nephrotic A 45 y.o. man with HTN, 2+B LE edema, rapidly rising Cr and the following UA. What is the dx? a) b) c) d) ATN Acute Glomerulonephritis Acute Interstitial Nephritis Nephrotic Syndrome Acute Post-Infectious GN Acute Post Strep. GN, Acute Proliferative GN • 8-14d after pharyn/skin inf w/Gr A B-hem strep, SBE, visceral abscess, OM, sepsis • Acute Nephritic Syndr: hematuria/HTN/edema/proteinuria • RBC casts, dysmorphic RBCs, + antistreptolysin ASO/streptozyme titer, low CH50/C3 • Pathology – LM –enlarged, hypercellular glomeruli with endo/mes cell prolifer. – IF –IgG, C3; coarsely gran along GBMs – EM –subepithelial “hump-like” deposits • Clinical Course/Tx – 5% will progress to RPGN, 70% will recover – Abx are not helpful except for ? family members – Tx is supportive Nephritic Nephrotic • • • • • • • • • • • Hematuria Proteinuria Hypoalbuminemia GFR↓, Cr↑, BUN↑, Oliguria Edema (salt/water retention) Hypertension Proteinuria >3.5g/day Hypoalbuminemia <3gm/dl General edema Hyperlipidemia Lipiduria Causes of Nephrotic Syndrome Primary Glomerular Disease Children(%) Membranous GN 5 40 Minimal Change GN 65 15 Focal Segmental GN 10 15 MPGN 10 7 Other GN 10 23 Systemic Diseases Diabetes Mellitus Amyloid Systemic Lupus Erythematosus Adults(%) Complications of Nephrotic Syndrome • Infections – Peritonitis, cellulitis, sepsis • Thrombosis – DVT, renal vein, arterial (kids) • AKI • Accelerated atherogenesis • Protein depletion Syndromes of Renal Diseases • • • • • • Acute Kidney Injury Nephritic syndrome Nephrotic syndrome Asymptomatic proteinuria Chronic Kidney Disease/ESRD Asymptomatic hematuria • • • • • • Urinary tract infection Nephrolithiasis Tumors Electrolyte disturbances Acid-Base problems Hypertension Isolated Asymptomatic Proteinuria Dipstick positive but no hematuria, pyuria • R/o fever, exercise, UTI, CHF induced proteinuria •  first AM spot U protein/creatinine (Up/c) NKF of Hawaii, Spring 2007 • Estimate GFR or measure creatinine clearance (Ccr) Up/c < 3.5 and nl GFR or Ccr Non Nephrotic Proteinuria Up/c > 3.5 and/or ↓GFR or Ccr Nephrotic Proteinuria with or w/o CKD  overnight recumbent Up/c • Nephrology consult esp if no DM, HTN • Serologic tests and/or renal biopsy Up/c < 0.2 (neg) Up/c = 0.2-0.5 Up/c > 0.5 Orthostatic Proteinuria Tubular or Early Glom Proteinuria Glom Proteinuria Recheck 1y UPEP x 1 to r/o protein dycrasia Up/c spot AM, UA, GFR, BP q6 mo Up/c stable, nl UA, GFR, BP consider Up/c ↑, ↓GFR, ↑ BP Progressive Proteinuria +/- CKD BP control, dietary Na, protein restrictions, consider ACEI/ARB, monitor q6-12 mo Albuminuria: New Risk Factor/Marker • High Prevalence: • 7% of the general population • 20% hypertensive population • 40% diabetic population • Easy and cheap to measure • Mild decrease in GFR and Microalbuminuria can be signs of mild CKD Predicts later development of heart disease, stroke and diabetes Definitions of Normal & Abnormal Urine Albumin Dipstick Protein Spot Collection 24hr Alb mg Prot Alb 24hr Timed Prot coll. mg µg/min Normal - - <0.03 or <30mg alb/g Cr <30 <150 <20 Microalbuminuria - + 0.03-0.3 or 30-300mg alb/g Cr 30-300 <500 20-200 Macroalbuminuria + + >0.3 or >300 mg alb/g Cr >300 >500 >200 Basi et al, AJKD. Vol 47, No 6 2006: 927-946 Vascular Diseases • Microvascular – Benign nephrosclerosis – Malignant hypertension/Malignant nephrosclerosis – Thrombotic microangiopathies • Macrovascular – Aortic aneurysm – Renal artery dissection or thrombosis – Renal vein thrombosis – Atheroembolic disease Thrombotic Microangiopathy (Microvascular AKI) • Morphologic finding in several diseases – Platelets form thrombi, deposit in kidneys – Glomerular capillary occlusion/thrombosis • Microangiopathic hemolytic anemia Thickening of the arterial wall, hyperplastic arteriolitis. The arteriole has an "onion skin" appearance • HUS, TTP, Malignant HTN, Systemic sclerosis • Plasma exchange, steroids, IVIG, splenectomy Fibrinoid necrosis of small arteries. The damage to the arteries leads to formation of pink fibrin- hence the term "fibrinoid" A 49 y.o. woman with Breast Cancer, s/p chemo with weakness, fever, rash. WBC 16.4, Hct 22, Platelets 55, Cr 3.2, LDH 5750, CK 550. UA 3+ prot, 2+blood, RBC. What is the dx? a) b) c) d) Acute Glomerulonephritis TTP (Thrombotic Thrombocytopenic Purpura) Nephrotic Syndrome Rhabdomyolysis A 49 y.o. woman with BC, s/p chemo w/weakness, fever, rash. WBC 16.4, Hct 22, Plat 55, Cr 3.2, LDH 5750, CK 550. UA 3+ prot, 2+blood, RBC. What is the dx? What test do you order next? – Order blood smear to r/o TTP a) b) c) d) Acute GN TTP Nephrotic Syndrome Rhabdomyolysis • TTP associated with malignancy, chemo • TTP may mimic GN on UA (RBCs, WBCs) • Thrombocytopenia, anemia not consistent with nephrotic/nephritic syndrome • New CK in the thousands to cause ARF Macrovascular ARF • • • • • Aortic Aneurysm Renal artery dissection or thrombosis B Renal artery stenosis Renal vein thrombosis Atheroembolic disease – New onset or accelerated HTN? – Abdominal bruits, reduced femoral pulses? – Vascular disease? – Embolic source? A 68 y.o. male s/p cardiac cath 4 days ago, now with Cr 1.6 (0.9 at baseline) and reddish-purplish mottling of the skin. What is the dx? a) b) c) d) Renal Artery Stenosis Contrast-Induced Nephropathy Abdominal Aortic Aneurysm Cholesterol Atheroemboli Atheroembolic ARF • Occurs after intravascular procedures (cardiac cath, CABG, AAA) – emboli of fragments of atherosclerotic plaque from aorta, other large arteries • Dx – Hx and PE-evidence of other emboli • CVA, ischemic digits, “blue toe” syndrome/Livedo Reticularis, mesenteric ischemia – Low C3 and C4, eosinophilia, eosinophiluria, rarely WBC casts – Renal bx- rarely • Tx: supportive Acute Renal Infarct Acute Kidney Injury: Work-up Chem 7 Serum Cr • Falsely ↑ with Septra, Cimetidine • Small ↑ reflects large ↑ GFR BUN/Cr Ratio • Ratio 20:1- pre-renal FeNa <1%: PRERENAL ATN (contrast, myoglobin) Glomerular or vascular injury FeNa >2%: ATN -damaged tubules can't reabsorb Loop diuretics cause natriuresis Steroids, GIB, catabolic state, hypovolemia • Ratio 10:1- intrinsic BUN generally follows Cr ↑ Other tests: Urine • Lytes, osmolality, creat, protein • Urine sediment: casts, cells • FeNa = (urine Na x plasma Cr) (plasma Na x urine Cr) • • • • • • • • Renal US 24 hr urine for protein & creatinine UPEP/SPEP Cholesterol, albumin, glucose ANA panel, ANCA, HIV, Hepatitis B/C, ASO, PSA Post-void residual or catheterization Renal biopsy Treatment of ARF • • • • • • • Eliminate the toxic insult Hemodynamic support Respiratory support Fluid management Electrolyte management Medication dose adjustment Dialysis A 40 y.o. man with Rhabdo with K 5.9 • Is it real? Pseudohyperkalemia • Too much intake Iatrogenic, salt substitute • Too little excretion Renal failure Drugs that block renal K excretion • ACEIs/ARBs, NSAIDs, Septra, Heparin • Shift Acidosis, hyperglycemia, muscle injury (rhabdomyolysis) Hemolysis, very high WBC (leukemia), very high platelet count What if K is 7.4? • Highly arrhythmogenic Progressive EKG changes • Peaked T waves → Widened QRS → Sinus wave • Emergent IV calcium gluconate • Urgent IV HCO3 IV glucose and insulin • Timely Kayexalate Furosemide Dialysis Indications for Dialysis • Hyperkalemia • Volume overload (resistant to diuresis) • Metabolic acidosis • Uremia – Mental status changes – Seizures – Pericarditis – Uncontrolled bleeding • Toxins removable by dialysis Syndromes of Renal Diseases • • • • • • Acute Kidney Injury Nephritic syndrome Nephrotic syndrome Asymptomatic proteinuria Chronic Kidney Disease/ESRD Asymptomatic hematuria • • • • • • Urinary tract infection Nephrolithiasis Tumors Electrolyte disturbances Acid-Base problems Hypertension Prevalence of kidney failure 1996 USRDS, 2007 Prevalence of kidney failure 2006 USRDS, 2007 Chronic Kidney Injury, ESRD The tip of the iceberg . . . 350,000 dialysis patients 30 million Americans with CKD ESRD by Dx ESRD = End Stage Renal Disease USRDS 2009 Diabetic Nephropathy • • • • 50% of DM1 & 40% DM2 patients Progressive proteinuria; initially- increased GFR 30% of pts develop ESRD? Diabetic Kidney Disease Hyaline nodules – Glomerulosclerosis, arteriolosclerosis → Hypertension – Pyelonephritis, Papillary necrosis • Test for microalbuminuria (30-300 mg/day) – yearly at 5 years from dx for Type 1, dx for Type 2 • Tx: – – – – ACEIs/ARBs BP Control BS Control Tx of proteinuria KW nodules Autosomal Dominant PKD • Common 1:1,000 • 10% of all transplant/dialysis patients • ADPKD-1 gene (polycystin) mutation in 85% • Symptoms appear in adult life Bilaterally enlarged kidneys (>3,000g) Liver (30%), splenic (10%) and pancreatic cysts (5%), cerebral aneurysms (20%), diverticuli • Renal failure 5-10 years thereafter 1 in 7 Adult Americans Have Chronic Kidney Disease (CKD) CKD Stage Kidney damage for ≥3 mo eGFR < 60ml/min/1.73m2 albuminuria, hematuria Number of Individuals 1 Albuminuria with nl or increased kidney function (≥90) 5.6 million 2 Albuminuria with mildly reduced kidney function ( 60-89) 5.7 million 3 30-59 7.4 million 4 15-29 300,000 5 <15 or dialysis 431,284 eGFR = estimated glomerular filtration rate. Coresh et al, J Am Soc Nephrol. 2005;16:180-188 eGFR (mL/min/1.73 m2) Chronic Kidney Disease • NO SYMPTOMS • • • • • • • General – weakness, fatigue, pruritis C.V. – hypertension, pericarditis G.I. – anorexia, nausea, vomiting, diarrhea CNS – lethargy, confusion, coma, neuropathy, asterexis Muscles – twitching, weakness Bones – osteodystrophy Metabolic – acidosis, P↑, K↑, BUN↑, Cr↑ • Endocrine – parathyroids↑, vit D def Chronic Kidney Disease Premature Death from Cardiovascular Disease Kidney Failure Foley, Foley,RN, RN,etetal,al,Am AmJ JKidney KidneyDis Dis1998;32(suppl 1998;32(suppl3):S112-S119 3):S112-S119 How to Test for Chronic Kidney Disease • Blood Pressure Measurement • Estimated GFR from serum creatinine using the MDRD prediction equation • Urine microalbumin with a microalbumin dipstick or “spot” urine albumin to creatinine ratio or standard dipstick *24 hour urine collections are NOT needed 1 Bouleware, et al., 2003 At what level of Creatinine does a 65y.o diabetic, hypertensive white woman weighing 50 kg have CKD? • 77% said: Creatinine > 1.5 mg / dl GFR = 37 mL/min/ 1.73 m2 Ccreat = 30 mL/min • Creatinine = 1.0 for GFR = 59 mL/min/1.73 m2 • MDRD formula uses creatinine, age, gender, race, normalized to average adult surface area http://www.kidney.org/prifessionals/kdoqi/gfr calculator.cfm Nat Kid Ed Prog, 2005 Intervention Makes a Difference • • • • • • • • • • BP less than 130/80 Use of ACEI/ARB Treatment of proteinuria Treatment of diabetes Attention to nutrition Treatment of anemia Treatment of hyperphosphatemia Treatment of hyperlipidemia and other CV risk factors Referring patients to a nephrologist Proactive permanent AV fistula placement Identifying Kidney Disease – Protects the Heart • Assess all patients for presence of CKD risk factors • Screen all patients with CKD risk factors for CKD • Identify etiology of CKD • Evaluate all CKD patients for CKD complications • Treat CKD-associated abnormalities both to optimize cardiovascular status and to slow CKD progression and Kidney Failure • Consult with a nephrologist as needed A 58 y.o. Caucasian male with a solitary kidney, referred for primary care. PMH: DM X 20 years, diabetic retinopathy, HTN, OA, s/p nephrectomy after trauma. • Meds: ASA 81 mg qd, Lisinopril 5 mg qd, HCTH 25 mg qd, Simvastatin 10 mg qd, NPH 40u BID • PE: 149/94, HR 74, 1+ edema • Labs: Na 139, K 5.0, Bun 66, Cr 2.5, Bicarb 27, Glu 194 Microalbumin/creat ratio: 950 mg/g creatinine Hgb 8.1, Iron 45, % sat 18, ferritin 95 iPTH 125, PO4 5.6, Ca 9.0, Alb 4.5 Our Patient • CKD risk factors: – – – – • Screen for CKD: – – – • Diabetes Hypertension Solitary kidney OA ? NSAIDs BP 149/94 Creat 2.5, eGFR 25 cc/min/1.73m2 Alb/Crea 950 mg/g creatinine Etiology of CKD: CKD and Diabetes ? Diabetic nephropathy K/DOQI CKD Staging Requires 2 or more GFR, 3 or more months apart GFR 90 60 Other markers of kidney disease: proteinuria, hematuria, anatomic 1 2 30 Complications Possible 15 Complications Evident Renal Replacement 4 5 3 CKD Stages Evaluate All CKD Patients for CKD Complications • CVD, HTN, Proteinuria, Volume overload-may be present at any eGFR • Anemia, Metabolic Bone Disease, Acidosis, Hyperkalemia, Malnutrition, Neuropathy-often develop once eGFR less than 60ml/min/1.73m2 Our Patient • HTN & Volume Management • Cardiovascular Disease 149/94, edema ? BP is associated with • Rate of renal decline and risk of ESRD • Stroke, myocardial infarction, & heart failure Patients with Stage 4 CKD (eGFR < 30ml/min/1.73m2) • At high risk of deterioration in renal function • Need counseling about modes of ESRD care, including hemodialysis, peritoneal dialysis, and transplantation • Need to be evaluated to construct an AV fistula eGFR is less than 25 ml/min Serum creatinine is greater than 4mg/dl Guideline 8, KDOQI 2002 Primary Care Practitioners Have a Key Lifesaving Role in Detecting Chronic Kidney Disease— a Silent Heart Killer • 1 in 7 Americans have CKD • CKD is a known risk factor for CVD • Most patients with CKD die from CVD before they develop Kidney Failure Syndromes of Renal Diseases • • • • • • Acute Kidney Injury Nephritic syndrome Nephrotic syndrome Asymptomatic proteinuria Chronic Kidney Disease/ESRD Asymptomatic hematuria • • • • • • Urinary tract infection Nephrolithiasis Tumors Electrolyte disturbances Acid-Base problems Hypertension 55 y.o. AA male with a hx of HTN comes after routine urinalysis done for life insurance showed 2+ hematuria and 1+proteinuria. • PE: BP 118/57, HR 63, o/w negative • Labs: Repeat UA 2+ blood Urine culture negative R Cohen, R Brown, NEJM 2003, 348-23 R Cohen, R Brown, NEJM 2003, 348-23 Dipstick positive for blood Hematuria Check U microscopy RBCs > 2 RBC/HPF Yes = Hematuria No = Myoglobinuria or Hemoglobinuria Check: • CPK • Myoglobin • U free hemoglobin With pyuria, bacteriuria = UTI No RBC casts No dysmorphic RBC No bacteriuria Antibiotic Rx if appropriate Urology evaluation If urological w/u – Resolution Persistant Hematuria With: Dysmorphic RBC, RBC casts, Proteinuria or ↓GFR Nephrology consult Possible renal biopsy NKF of Hawaii, Spring 2007 Do all patients with hematuria need to be evaluated by a nephrologist? • • • • • Dysmorphic RBC RBC casts Proteinuria Decreased GFR Hypertension Consultation with a nephrologist should be considered • GFR< 30ml/min/1.73m2 (stage 4)  refer for RRT preparation & transplant evaluation • Rapid progression (loss of GFR>4 ml/min/1.73m2 per year) • Diagnosis is unclear • Co-managing of CKD complications • Difficulty controlling blood pressure • Proteinuria >1g per day • Hematuria with RBC casts/dysmorphic RBCs, proteinuria, Htn Syndromes of Renal Diseases • • • • • • Acute Kidney Injury Nephritic syndrome Nephrotic syndrome Asymptomatic proteinuria Chronic Kidney Disease/ESRD Asymptomatic hematuria • • • • • • Urinary tract infection Nephrolithiasis Tumors Electrolyte disturbances Acid-Base problems Hypertension Acute Pyelonephritis • Bacterial infection (E. coli 80%) • Ascending/hematogenous • Lower UTI precedes renal infection • Fever, flank pain, neutrophilia • Leukocyte casts in urine • Healing - recurrence→ chronic pyelonephritis Acute Pyelonephritis with papillary necrosis (diabetes) Predisposing Factors for Pyelonephritis • Urolithiasis • Reflux • Infections of lower UT • Neoplasms • Ureteric, vesical, prostatic • External compression • Pregnancy, retroperitoneal fibrosis Urolithiasis • Incidence: 1-5%, males predominance • Etiology: environmental, metabolic, infectious • Clinical features Ca oxalate is the most common Silent/ Renal colic/ Dull ache in loins Gross or micro hematuria May recur Complications: Obstruction/ hydronephrosis/ hydroureter/ recurrent UTI • Treatment Adequate hydration, low salt diet Tx of metabolic abnl (hypocitraturia, hypercalciuria) Surgery, lithotripsy Hydronephrosis Renal Cell Carcinoma— Most Common Renal Tumor • Peak age – 60y, M:F = 3:1 • Risk factors • Tobacco; Obesity, Genetics • VHL gene, familial • Classical triad < 10% – Hematuria, flank pain, mass • Hematuria 50% – Most common symptom • Metastases – Hematogenous/local abdominal • Paraneoplastic syndromes – PTH, Epo, amyloid • 5 year survival 40%