Renal Diseases. Ruediger W. Lehrich, M.D. Duke University Medical Center, Division of Nephrology

Transcription

1 Renal Diseases Ruediger W. Lehrich, M.D. Duke University Medical Center, Division of Nephrology

2 Disclosures none

3 Learning Objectives Basic review of common renal diseases: Acute renal failure Chronic kidney disease Glomerulonephritis and nephrotic syndrome Polycystic kidney disease Obstructive Nephropathy Renal vascular disease Hypertension Hyponatremia Hyperkalemia Acid base disorders

4 How Do We Measure Renal Function Glomerular filtration rate (GFR) volume of plasma water filtered per unit of time. Expressed as ml per minute. Most commonly used marker: creatinine and blood urea nitrogen (BUN). Elevation in creatinine or BUN corresponds to decrease in renal function.

5 How Do We Define Acute Renal Failure? Rise of serum creatinine of at least 0.3 mg/dl from baseline in 8 hours. Decrease in urine output to less than 0.5 ml/kg/h for more than 6 hours. Oliguria < 400 ml/24 hr, Anuria < 100 ml/24 hr. Risk factors: CKD, diabetes, heart failure, liver failure, hypovolemia and age <50 years.

6 Categories of Renal Failure 1Prerenal Sudden drop in blood pressure Interruption of blood flow to the kidneys 2Intrarenal Direct damage to kidneys Inflammation Acute GN or IN Toxins and Drugs ATN 3Postrenal Obstruction of urine flow Enlarged prostate Malignancy 2 3 1

7 Work Up Of Acute Renal Failure 1History Exposure to toxin and medication Systemic manifestation of disease 2Physical Examination Blood pressure, orthostasis, neck veins Rash, presence of a friction rub Urine output and urinary retention 3Laboratory analysis of the serum Creatinine and BUN Serologies 4Urine analysis Presence of proteinuria or hematuria 5 Imaging

8 Case: 25 y/o woman presented to her PCP with urinary urgency and dysuria 5 days ago. She was given Bactrim DS 1 qd x 7 days (first exposure to this drug). After three days she returns with a rash.

9 Case: Cr 3.5 mg/dl, CBC with 13% eosinophils on differential Acute renal failure secondary to allergic interstitial nephritis

10 Chronic Kidney Disease Definition: Kidney damage or decreased kidney function lasting greater than 3 months. Prevalence: 10-12% Primary causes: diabetes mellitus, hypertension Risk factors: Proteinuria Hypertension African American race Male gender Obesity Hyperlipidemia Smoking Phosphate retention Metabolic acidosis

11 Chronic Kidney Disease At risk for progression Transplant Dialysis Stage 1 Kidney damage Normal function Stage 2 Mild kidney damage Stage 3 Moderate kidney damage Stage 4 Severe damage Stage 5 Kidney Failure Glomerular Filtration Rate ml/min No symptoms moderate severe

12 Pitfalls of Serum Creatinine

13 Chronic Kidney Disease: General Management Addressing reversible causes: Decreased renal perfusion Nephrotoxic drugs Urinary tract obstruction Controlling progression of CKD: Blood pressure control: <130/80 Address the underlying cause: hyperlipidemia, hyperglycemia, smoking Careful dosing of medications Referral to Nephrology

14 Chronic Kidney Disease: Complications Volume overload Hyperkalemia Metabolic acidosis Hyperphosphatemia Renal osteodystrophy Hypertension Anemia Na restricted diet, diuretics K restricted diet, caution with K-increasing medications Bicarbonate supplementation Phosphorus restricted diet, oral phosphate binders Due to secondary hyperparathyroidism suppress parathyroid hormone Goal blood pressure generally 130/80 with ACE inhibitor or ARB if proteinuria is present Assess for iron deficiency, consider Epogen

15 End Stage Renal Disease or ESRD Indications for renal replacement therapy When to start: Symptoms are present, around 5-8 ml/min egfr What to look for: altered mental status, poor appetite, nausea, dysgeusia, poor energy, weight loss, pericarditis, pruritus Modalities of renal replacement therapy Hemodialysis Peritoneal dialysis Home hemodialysis

16 Incidence of ESRD

17 Incidence of ESRD in the U.S.

18 Causes of ESRD in the U.S.

19 Glomerulonephritis and Nephrotic Syndrome Major cause of chronic kidney disease Inflammation of glomeruli Injury can be: Normal Glomerulus primary epithelial (podocytes, basement membrane) vascular (endothelial) mesangial Inflamed Glomerulus

20 Glomerulonephritis and Nephrotic Syndrome Nephrotic Syndrome Proteinuria > 3.5 grams/day Hypoalbuminemia Edema Hyperlipidemia Nephritic Syndrome Hematuria with RBC Hypertension Oliguria Proteinuria < 1.5 grams/day Rapidly Progressive Glomerulonephritis Rapid progression to acute renal failure if untreated Inflammation and Proliferation

21 Nephrotic Syndrome: Minimal Change Disease Normal light microscopy, electron microscopy with fusion of epithelial foot processes Most common cause of nephrotic syndrome in children Idiopathic, drugs (NSAIDs), hematologic malignancies

22 Glomerulonephritis: Membranous Nephropathy Most common nephropathy in adults Autoimmune (Anti-PLA2R- Ab), malignancies, infections spike-and-dome pattern of granular IgG and C3 deposits in the basement membrane 1/3 of cases progress to ESRD

23 Glomerulonephritis: FSGS Lesions are focal (<50% of glomeruli) and segmental (<50% of glomerular tuft) Most common GN in African Americans Idiopathic, genetic, associated with infections (HIV), drugs (heroin), hyperfiltration (reflux nephropathy, renal dysplasia, obesity)

24 Glomerulonephritis: IgA nephropathy Most common GN worldwide Affects children and young adults, male preponderance Associated with upper respiratory or GI infections and Henoch-Schönlein purpura (IgA vasculitis) Immunofluorescence: IgA in the glomerular mesangium IgA Deposition

25 Glomerulonephritis: Goodpasture Syndrome Pulmonary-renal syndrome Anti-GBM-antibody formation leads to renal failure and pulmonary hemorrhage Linear anti-gbm deposits on immunofluorescence

26 Glomerulonephritis: Nephrotic versus Nephritic Nephrotic Minimal change disease FSGS Membranous nephropathy Diabetes mellitus Nephrotic/Nephriti c Lupus nephritis IgA nephropathy Nephritic post-infectious GN Goodpasture s syndrome ANCA vasculitis Proteinuria Hematuria

27 Polycyctic Kidney Disease Most common inherited kidney disease Genetic disorders associated with mutations in either Polycystin-1 (PKD-1) or Polycystin-2 (PKD-2) genes Gradual cyst growth worsens renal function Renal Failure Hallmark Findings Hypertension Bilateral Enlarged Kidneys Flank Pain Hematuria Cyst infection and bleeding

28 Polycyctic Kidney Disease Other Clinical Findings: Kidney Stones Intracerebral Aneurysm Liver Cysts (also Pancreas, Spleen, Ovarian cysts) Diagnosis by Ultrasound: Number of Cysts needed for Diagnosis increases with Age Therapy: Blood pressure control Treat cyst infection with antibiotics for 2 weeks

29 Polycyctic Kidney Disease Simple Cysts versus Complex Cysts Simple Cysts Complex Cysts (Potential Malignancy) Echogenicity Echo Free Mixed Echogenicity Walls Smooth, Thin Irregular, Thick Demarcation Sharp Lower Density on Back Transmission Good Debris in Cyst

30 Other Cystic Kidney Diseases Findings Tuberous Sclerosis Von Hippel Lindau Medullary Sponge Kidney Images Inheritance Pattern Autosomal Dominant Autosomal Dominant Not Inherited Clinical Syndromes Seizures; Multiple hamartomas; Renal angiomyolipomas CNS hemangioblastoma, renal cell cancer, tumors in multiple other organ systems Beckwith- Wiedemann syndrome; Congenital hepatic fibrosis

31 Obstructive Nephropathy Definitions: Hydronephrosis - Dilation of the renal pelvis or calyces Obstructive uropathy - functional or anatomic obstruction of urine flow at any level of the urinary tract Obstructive nephropathy acute or chronic renal failure in the setting of obstruction

32 Obstructive Nephropathy: Etiology Intrarenal etiologies Polycystic kidney, fibrous obstruction at ureteropelvic junction, Neoplastic process including multiple myeloma Infection Renal calculus Ureteral etiologies Ureterovesical reflux Neoplastic process Infectious etiologies (Schistosomiasis) Miscellaneous - Retroperitoneal fibrosis, radiation therapy, pregnancy Bladder and Urethra Posterior urethral valve, phimosis, urethral stricture Bladder carcinoma, prostate carcinoma, carcinoma of urethra Prostatitis Benign prostatic hypertrophy, neurogenic bladder

33 Obstructive Nephropathy: Diagnosis

34 Obstructive Nephropathy: Timeline Duration of Obstruction: 42 hours - Dilation of the pelvis and ureter and blunting of the papillary tips. 7 days - Increased pelviureteric dilation and weight. Parenchyma is edematous days - External dimensions of kidneys are similar but the cortex and medullary tissue is diffusely thinned 6 weeks - Enlarged,cystic appearing, weight is less than non-obstructed kidney

35 Renal Vascular Disease Renal Artery Stenosis: Narrowing of the renal arteries associated with renal failure This occurs at the ostia of one or both renal arteries Renal artery stenosis is associated with hypertension and CKD Medical treatment includes statins, antiplatelet therapy, and blood pressure control Renal artery angioplasty is not helpful Fibromuscular dysplasia

36 Renal Artery Stenosis: Lack of Benefit with Angioplasty Cooper, NEJM 2014

37 Renal Vascular Disease Cholesterol Embolic Disease Occurs spontaneously and after endovascular or surgical manipulation of an atheromatous aorta. The prevalence is proportional to the burden of erosive atherosclerotic plaque in the aorta proximal to the renal arteries. Cholesterol crystals cause inflammatory reaction in arteries eventually leading to fibrosis and renal failure.

38 Hypertension Major healthcare burden that affects approximately 40% of the global population Largest risk factor for cardiovascular disease, which is the leading cause of death worldwide. Definition of hypertension: abnormally elevated arterial blood pressure Systolic Blood Pressure (mmhg) Diastolic Blood Pressure (mmhg) Normotension <120 and <80 Pre-hypertension or Stage 1 hypertension or Stage 2 hypertension 160 or 100

39 Primary Hypertension Hypertension with no identifiable cause Also referred to as essential hypertension accounts for 90 % of cases Risk factors include: age (men > 45, women > 55) race (blacks > whites) gender (men > women) above normal body weight family history lifestyle (excess salt or alcohol, stress, physical inactivity)

40 Secondary Hypertension Hypertension from an identifiable cause Accounts for 10% of cases Causes include: Kidney disease Primary aldosteronism Obesity Obstructive sleep apnea Thyroid disease Hyperparathyroidism Pheochromocytoma Cushing s syndrome Medications/drugs Coarctation of the aorta

41 Hypertension: Targets and Treatment Goal blood pressure for the general population: < 140/90 mmhg Lower targets for patients with additional risk factors for cardiovascular disease, such as diabetics and patients with chronic kidney disease. Life style modification: Weight loss Dietary Approaches to Stop Hypertension (DASH) diet Physical activity Sodium restriction Limited alcohol intake Minimize stress Medication: First line therapy almost always a diuretic Spironolactone to treat therapy resistant hypertension

42 Hyponatremia - Pathophysiology

43 Hyponatremia - Pathophysiology Hyponatremia is caused by the gain of water, not a loss of salt Water Gain via ADH

44 Approach to Hyponatremia Extracellular Status Volume Status Low Normal High GI Fluid Loss Adrenal Insufficiency Diuretics Cerebral Salt Wasting Burns & 3 rd Space Fluid Loss Marathon Runners SIADH Glucocorticoid Deficiency Hypothyroidism (Reset Osmostat) Edema-forming States Heart Failure Cirrhosis Status Status Status

45 Approach to Hyponatremia Extracellular Status Volume Status Low Normal High GI Fluid Loss Adrenal Insufficiency Diuretics Cerebral Salt Wasting Burns & 3 rd Space Fluid Loss Marathon Runners SIADH Glucocorticoid Deficiency Hypothyroidism (Reset Osmostat) Edema-forming States Heart Failure Cirrhosis Status Status Status Status Status Status Increased ADH: appropriate Increased ADH: inappropriate Increased ADH: maladaptive

46 Approach to Hyponatremia Extracellular Status Volume Status Low Normal High GI Fluid Loss Adrenal Insufficiency Diuretics Cerebral Salt Wasting Burns & 3 rd Space Fluid Loss Marathon Runners SIADH Glucocorticoid Deficiency Hypothyroidism (Reset Osmostat) Edema-forming States Heart Failure Cirrhosis Status Status Status Status Status Status Increased ADH: appropriate Increased ADH: inappropriate Increased ADH: maladaptive Volume Status Resuscitation Decrease Status AHD Action? Status Decrease AHD Action?

47 Case: 64-year-old man with recently diagnosed metastatic small cell carcinoma of the lung presented to the emergency department with a history of abdominal pain, fatigue and confusion. Admitted several times over the last three months due to recurrent episodes of hyponatremia, having failed to respond to water restriction as well as discontinuation of hydrochlorothiazide and fluoxetine.

48 Case: Initial laboratory: Na mmol/l BUN 9 mg/dl Crea 0.9 mg/dl S osm 256 mosm/kg H 2 O U Na 89 mmol/l U Osm 480 mosm/kg H 2 O. Plasma cortisol and a thyroid function panel were normal. SIADH secondary to small cell lung cancer.

49 Serum Sodium (meq/l) Urine Osm (mosm/kg) Case: Serum Sodium and Urine Osmolarity Fluid Restriction Vasopressin Receptor Antagonist 145(long-term 600 oral therapy) Serum Na U osm Time (Days)

50 Hyperkalemia Potassium is the primary intracellular cation. Ratio of intracellular to extracellular potassium determines membrane electrical activity. Causes of hyperkalemia: Increased potassium intake Transcellular shifts Cell lysis due to tissue damage Advanced renal insufficiency Potassium-sparing diuretics Decreased distal delivery of glomerular filtrate Aldosterone insufficiency Type IV renal tubular acidosis

51 Case: 62 year old woman h/o ESRD who presented with progressive leg weakness for one day. VS: HR 16-20, BP 213/88, RR 16, SaO2 100% on 4L NC, T 35.4 Phys. Exam: Somewhat confused, marked regular bradycardia, R. femoral PC, unable to move lower extremities. Na mmo/l, HCO 3 24 mmo/l, Cl mmo/l, WBC 6, K mmo/l

52 Case:

53 Treatment of Hyperkalemia Mechanism Treatment Onset (Duration) I. Stabilizes cardiac membranes Calcium Immediate (15-30 min) II. Shifts potassium intracellularly III. Removes potassium Insulin and glucose Beta 2 -adrenergic agonist Sodium bicarbonate Sodium polystyrene sulfonate Loop diuretic Hemodialysis min (2-3 hours) min (2-3 hours) Delayed onset 4-6 hours 1 hour Immediate

54 Acid Base Disorders: Definition Acidosis: A process which lowers the extracellular fluid ph (raising the hydrogen ion concentration) ph <7.40 Alkalosis: A process which raises the extracellular fluid ph (lowering the hydrogen ion concentration) ph >7.40

55 Acid Base Disorders: Definition Respiratory A disturbance that refers to a acid base disorders initiated by changes in pco 2 Metabolic A disturbance that refers to an acid-base disorders initiated by changes in HCO3 -

56 Acid Base Disorders: Definition Metabolic Acidosis: A disorder with a low ph and a low bicarbonate concentration Metabolic Alkalosis: A disorder with a high ph and and a high bicarbonate concentration Respiratory Acidosis: A disorder with a low ph and a high pco2 Respiratory Alkalosis: A disorder with a high ph and a low pco2

57 Case: 42 year old woman with Type 1 DM presents to the ER after running out of insulin for 3 days. Na mmol/l HCO 2 6 mmol/l Glucose greater than 600 mg/dl ABG: ph 7.19, pco 2 18 Acidosis (ph 7.19), Metabolic HCO3 6 mmol/l pco 2 is adequately reduced Compensated metabolic acidosis

58 Questions?