Nephrology Board Review Outline Hypertension Kidney in pregnancy Clinical Evaluation of Kidney AKI CKD Glomerulonephritis Electrolytes Outline Hypernatremia,hyponatremia Hypokalemia, hyperkalemia Hypercalcemia, hypocalcemia Nephrolithiasis Genetic diseases of Kidney Renal Replacement Modalities JNC Stratification BP Normal SBP (mm Hg) < 120 DBP (mm Hg) < 80 Pre- Hypertension 120-139 80-89 Stage One 140-159 90-99 Stage Two >160 100 Office Bp measurements Use auscultatory method with properly calibrated and validated instrument Patient should be seated for 5 minutes in a chair with feet rested on the floor and arm supported at chest level. Appropriate size cuff should be used to ensure accuracy. Atleast 2 measurements should be made. We should provide written and verbal confirmation of bp numbers and goal Ambulatory BP monitoring ABPM is warranted for evaluation of “white coat HTN” in the absence of target organ injury. ABPM values are lower than clinic settings. Awake, individuals with HTN have an average value >135/85 mm Hg and during sleep >120/75mm Hg. Bp drops by 10-20% during the night, and if not then it may signal CV disease. “Non Dippers” Lifestyle Modification Modification Approximate SBP reduction (range) Weight reduction 5–20 mmHg/10 kg wt loss Adopt DASH Diet 8–14 mmHg Dietary NA reduction 2–8 mmHg Physical activity 4–9 mmHg Moderation of alcohol consumption 2–4 mmHg Causes of Secondary HTN Renal disorders: parenchymal disease: GN, Nephrotic syndrome, PCKD, CKD; Renovascular Disease Endocrine Disorders: Pheo, Primary hyperaldosteronism, Cushings syndrome, Carcinoid, Hyperthyroid or hypothyroidism, Hyperparathyroidism, Acromegaly. Secondary HTN OSA Polycythemia Medications such as steroids, EPO, CSA, Prograf.. Stimulants/drugs/etoh Coarctation of Aorta, Liddle’s syndrome, Gordon’s syndrome, 11 Beta hydroxysteroid deficiency, Licorice, GRA Laboratory Evaluation Routine Tests EKG Urinalysis Blood glucose and Hct Serum Potassium, Creatnine and Calcium Fasting Lipid profile Optional Tests: urinary Albumin excretion More extensive tests are not warranted unless BP Control is not achieved. Principal Cell Algorithm for RX of Hypertension Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Without Compelling Indications With Compelling Indications Stage 1 Hypertension Stage 2 Hypertension (SBP 140–159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. (SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Heart Failure POST MI CAD risk DM CKD Recurrent Stroke Aldost Inhibitor CCB ARB Ace Inhibitor Beta Blocker Diuretics Compelling Indications Differential Diagnosis of Azotemia Etiologies of elevated Cr: Kidney disease Large Muscle mass, AA Medications that block creatnine secretion cimetidine, trimethoprim, probenecid Substances that interfere with creatnine assay- cefoxitin, flucytosine, acetoacetate, bilirubin Acute Kidney Injury Definition of Acute Kidney Injury Loss of renal function measured as GFR over hours to days Expressed clinically as the retention of nitrogenous waste products in the blood. Definitions Azotemia- accummulation of nitrogenous wastes Uremia- symptomatic renal failure Oliguria- urine output <400-500ml/24hrs Anuria- urine output<100ml/24hrs Causes of Anuria Obstruction (vast majority of patients with anuria) Bilateral renal cortical necrosis Fulminant glomerulonephritis (usually some type of rapidly progressive glomerulonephritis) Acute bilateral renal artery or vein occlusion (rare) Classification of the Etiologies of AKI Acute Kidney Injury Prerenal Acute Tubular Necrosis Intrinsic Acute Interstitial Nephritis Acute Glomerulonephritis Postrenal Acute Vascular Syndrome Intratubular Obstruction Differential Diagnosis of Acute Renal Failure Prerenal acute renal failure True intravascular depletion Sepsis, hemorrhage, overdiuresis, poor fluid intake, vomiting, diarrhea Decreased effective circulating volume to the kidneys Congestive heart failure, cirrhosis or hepatorenal syndrome, nephrotic syndrome Impaired renal blood flow because of exogenous agents Angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, CSA. Hypercalcemia. Abdominal compartment syndrome with increased renal vein pressures Diagnostic Criteria for HRS Major criteria: Low GFR (<40ml/min or cr>1.5mg/dl) Absence of shock, ongoing bacterial infection, treatment with nephrotoxins or volume loss No improvement with diuretics or volume expansion with 1.5L of isotonic saline Proteinuria<500mg/dl and no US evidence of obstruction or parenchymal dz. Diagnostic Criteria for HRS Minor criteria Urine volume <500ml/day UNa<10mmol/L Urine osm>plasma osm Urine rbc<50 per high power field Serum sodium <130 mmol/L Arroyo et al Hepatology 1996 AKI in Liver disease Pre renal azotemia HRS ATN Interstitial Nephritis Glomerular syndromes: IGA, cryoglobulinemia, MPGN, Membranous Nephropathy Precipitating factors for HRS SBP Severe Bacterial Infection GI Bleed Major surgery Aggressive diuresis Paracentesis Abdominal Compartment Syndrome Clinical setting Trauma patient following massive volume resuscitation, post liver tx, mechanical limitations to abd wall such as burn injuries, post surgery etc. Bowel obstruction or pancreatitis. Clinical manifestations include: respiratory compromise, decreased CO, intestinal ischemia, oliguric AKI Abdominal Compartment Syndrome Pathophysiology of AKI- Increased renal venous pressure, increased parenchymal pressure, decreased perfusion Diagnosis- suspect in distended abdomen. Excluded if bladder pressure<10 and dx when bladder pressure >25mm Hg. Treatment Abdominal decompression Differential Diagnosis of Acute Renal Failure Postrenal acute renal failure Benign prostatic hypertrophy or prostate cancer, cervical cancer, retroperitoneal disorders, pelvic mass or invasive pelvic malignancy, intraluminal bladder mass (clot, tumor or fungus ball), neurogenic bladder, urethral strictures intratubular obstruction (crystals or myeloma light chains), Intrinsic AKI ATN AIN AGN Acute vascular syndromes Intratubular obstruction Acute Interstitial Nephritis Acute Kidney injury due to lymphocytic infiltration of the interstitium Classic triad fever rash and eosinophilia (described in the methicillin patients and occurrs <30% of cases) Acute Interstitial Nephritis Drug induced PCN Cephalosporins Sulfa Rifampin Phenytoin Furosemide NSAIDS PPI Ciprofloxacin Malignancy Idiopathic Infection related Bacterial Viral Rickettsial TB Systemic diseases SLE Sjogrens syndrome TINU Common Drugs That Can Cause Allergic Interstitial Nephritis Allopurinol (Zyloprim) Cephalosporins Cimetidine (Tagamet) Ciprofloxacin (Cipro) Furosemide (Lasix) Nonsteroidal anti-inflammatory drugs Penicillins Phenytoin (Dilantin) Rifampin (Rifadin) Sulfonamides Thiazide diuretics Acute Interstitial Nephritis History Preceeding illness or drug exposure Physical exam Fever, rash Lab finding eosinophilia Urine findings Non nephrotic proteinuria Hematuria Pyuria Wbc casts eosinophiluria Acute Interstitial Nephritis Pearls NSAID AIN is often without urine eos. 3 sets of urine without eos has a NPV of >95% for AIN (other than from NSAIDs) Urine eos can be positive in pyelonephritis, GN, Radiation nephritis and AIN Acute Interstitial Nephritis Treatment Discontinue offending drug Steroid therapy may hasten recovery but no RCT only case cohorts. Acute Glomerulonephritis RPGN- 3 types 1. Ab mediated against basement membrane. Anti GBM dz 2. Ag-Ab complex deposit in the GBM: SLE, HepC, post strep, post infectious, endocarditis associated, IGA 3. Pauci immune: Wegner’s, Microscopic polyangiitis, Churg strauss Acute Glomerulonephritis Proteinuria and hematuria. Quantify the proteinuria. Acitve urinary sediment with dysmorphic red blood cells or rbc casts. Low complements in SLE, MPGN, post strep or endocarditis or infections. ANCA and Anti GBM titers. ANA Vascular Syndromes Macrovascular: Renal artery thromboembolism Renal artery dissection Renal vein thrombosis Microvascular Atheroembolic disease TTP HUS Atheroembolic disease Risk Factors: Atherosclerosis, HTN, HLP, DM Precipitating risk factors: Arterial catheterization, arteriography, anticoagulation, vascular surgery, thrombolytic surgery Atheroembolic disease General: fever, myalgias, weight loss Cutaneous: livedo reticularis, digital ischemia Neurologic- TIA, CVA, AMS, Spinal cord infarct GI- anorexia, bowel ischemia, pancreatitis, Muskuloskeletal- myositis Eyes- amaurosis fugax, retinal cholesterol emboli Atheroembolic disease Serum chemisterieselevated bun, cr, amylase, cpk, lfts Hematologyleukocytosis, eosinophilia, anemia, thrombocytopenia Serologies- increased esr and low complements. Urine- eosinophiluria, proteinuria, hematuria, pyuria Atheroembolic disease Treatment: Avoid anticoagulation Avoid vascular intervention Nutrition support Dialysis Intratubular Obstruction Intratubular crystal deposition Tumor lysis syndrome- acute urate nephropathy Ethylene glycol toxicity- calcium oxalate deposition Medication associated- indinavir, acyclovir Intratubular protein deposition- multiple myelom with bence jones protein deposition ATN Ischemic- prolonged prerenal azotemia, hypotension, hypovolemic shock, cardiopulmonary arrest, cardiopulmonary bypass Sepsis Nephrotoxins Drug inducedradiocontrast, aminoglycosides, ampho B, Cisplatinum Pigment nephropathy hemoglobinuria, myoglobinuria Nephrotoxins Acyclovir (Zovirax) Tenofovir Aminoglycosides* Amphotericin B (Fungizone) Angiotensin-converting enzyme inhibitors* Cancer drugs: cisplatin (Platinol AQ), ifosfamide (Ifex) Cocaine Cyclosporine (Sandimmune) Foscarnet (Foscavir) Heavy metals Myeloma light chains Nonsteroidal anti-inflammatory drugs* Oxalic acid Pentamidine (NebuPent, Pentam 300, Pneumopent) Pigment: hemoglobin, myoglobin Radiocontrast media* ATN Prevention of ATN Identification of high risk patients Timing of insult Repeated insults. Blood and Urine Studies to Distinguish Prerenal from Intrinsic Acute Renal Failure Type of renal failure BUN-to-creatinine Urine osmolality Prerenal acute renal failure Intrinsic acute renal failure >20:1 >500 mOsm <20:1 250 to 300 mOsm Fractional excretion of sodium* <1% >3% Findings on Urinalysis in the Broad Categories of Acute Renal Failure Prerenal acute renal failure Scant; few hyaline casts Postrenal acute renal failure Scant; few hyaline casts, possible red cells Acute tubular necrosis Epithelial cells, muddy-brown, coarsely granular casts, white blood cells, low-grade proteinuria Allergic interstitial nephritis White blood cells, red blood cells, epithelial cells, eosinophils, possible white blood cell cast, low to moderate proteinuria Glomerulonephritis Red blood cell casts, dysmorphic red cells, moderate to severe proteinuria, oval fat bodies Management of CKD Etiology of CKD/Progression Anemia Access Adequacy BP Bone Metabolism Cardiovascular Risk Diet/Nutrition Etiology/Progression In the MDRD study Rate of Progression of CKD varies based on : Underlying disease, proteinuria, Stage of CKD, comorbidities and treatments. Retrospective analysis of MRFIT data showed that :1+proteinuria-3.1%, 2+ 15.7%, GFR 60-30 2.4%, GFR <30 41% over a 10 year period. Access GFR <25ml/min or rapid progression consider placement of hemodialysis access. Transplant referral at GFR<30 and placement on transplant list at <20. AVF AVG Tunneled Catheter Periotenal dialysis Adequacy Is the GFR adequate to avoid: volume overload, uremic sxs- nausea, malnutrition, pericarditis, lethargy, hyperk, acidosis. Most common reasons to start- malnutrition and volume overload. GFR<15ml/min per NKF are indications to consider the risks and benefits to initiating dialysis. European Best Practice guidelines state GFR<6ml/min and consider at 8-10 40 1.0 0.9 A B 0.8 0.7 0.6 0.5 0 P-values: Overall <.001 A vs B =.013 A vs C <.001 B vs C <.001 C Incidence (%) Reduction in Survival due to CV Mortality Proteinuria and Risk of CV Mortality,Stroke, and CHD Events in Type 2 Diabetes 30 P<.001 for trends 20 10 0 0 10 20 30 40 50 60 70 80 90 Months A: UPC <150 mg/L B: UPC 150-300 mg/L CHD, coronary heart disease; UPC, urinary protein concentration. * Defined as CHD death or nonfatal MI. Adapted from Miettinen H et al. Stroke. 1996;27:2033-2039. Stroke CHD Events* C: UPC >300 mg/L IRMA 2 - Results % Reduction in Urinary Albumin Excretion % Reduction in UAER 0% -5% -2% -10% -15% -24% -20% -25% -30% -38% -35% -40% Placebo Irbesartan 150 mg Irbesartan 300 mg p < 0.001 for Irb 300 mg vs Irb 150 mg Adapted from Parving HH. et al. N Engl J Med 2001;345(12):870-878. 20 IRMA 2 Primary End Point: Time to Overt Proteinuria Control (n=201)* Irbesartan 150 mg/d (n=195)* Irbesartan 300 mg/d (n=194)* Patients (%) 15 RRR=39% P=.08 10 RRR=70% P<.001 5 0 0 3 6 12 Follow-up (mo) 18 22 24 RRR, relative risk reduction. Control defined as placebo. * Adjunctive antihypertensive therapies (excluding ACE inhibitors, ARBs, and dihydropyridine CCBs) could be added to all groups to help achieve target BP levels. Adapted from Parving H-H et al. N Engl J Med. 2001;345:870-878. 81 BP Per JNC VII ACEI/ARB preferred agents in CKD (even if not hypertensive but prot). Most prominent in patients on low sodium diet, on diuretics and volume depletion. Reduction in proteinuria and intraglomerular pressure. Antifibrotic effects Other agents BP Aggressive BP lowering effective in proteinuric (<1gm/day) patients. Response to reduction in proteinuria in multiple studies predicts a better outcome. BP control is important for CVD protection and renoprotection. Approach to the hyponatremic patient Hyponatremia High Osmolality Normal Osmolality Low Osmolality Hyponatremia with high or Nml Osmolality TRANSLOCATION GLUCOSE MANNITOL GLYCINE MALTOSE PSEUDOHYPONATRE PROTEIN LIPIDS Pseudohyponatremia Normally serum is 93%water and 7% lipids. If non aqueous portion of serum rose to 20% Serum measured Na would be: 150x0.8=120 as opposed to 150x0.93 Pseudohyponatremia Approach to the hyponatremic patient with Low plasma osm Hyponatremia with low Osm Normally Dilute urine <100mosm Psychogenic Polydipsia Uosm>100mosm Low Solute intake Low Solute intake Urine flow= urinary solute excretion urinary osmolality Sources of urinary solutes Psychogenic Polydipsia Usually acute Common in institutionalized schizophrenics Abnormal weight gains (as much as 10%) Episodic symptoms that resolve with water restriction Beer Potomania Large intake of fluid with beer as sole source of nutrition Beer sodium content <2meq/L Beer Potassium content 10-12meq/L Beer Potomania Assume Beer consumption of 5L Na intake 10mM K intake 50mM Obligatory urea excre 80mM V=Soluteexcretion Uosm 5=200 40 Approach to the hyponatremic patient with low plasma osm Low plasma osm Normally dilute urine Uosm<100 Uosm>100mosm Almost always vasopressin mediated Hyponatremia in Edematous disorders Reflects advanced disease and poor prognosis Decreased delivery to diluting sites Increased vasopressin levels Increased AQP2 expression Cerebral Salt wasting Most common in subarachnoid hemorrhage Increased ANP and BNP Loss of sodium, volume depletion which then leads to increased ADH. Different from SIADH as volume depleted. Treat with saline Features of SIADH Clinically euvolemic Uosm>100mosm Una=Na intake usually >20meq/L Low bun and Uric acid Malignancies and SIADH Most common with small cell lung ca (1015%) mRNA for AVP in tumor Head and neck tumors Other isolated cases Treatment of Hyponatremia Three key Questions How long has the hyponatremia been present? Does the patient have symptoms? Does the patient have risk factors for the development of neurologic complications? Duration of Hyponatremia acute <48hrs Severe brain edema Rapid correction is well tolerated BUT WHEN IN DOUBT…Treat as chronic Patients at increased risk for neurologic complications Post op menstruant females Elderly women on HCTZ Children Hypoxemic patients Psychogenic polydipsia Duration of Hyponatremia Chronic 48hrs or unknown duration Mild cerebral edema <10% Sensitive to correction Symptomatic vs Asymptomatic Symptomatic hyponatremia warrents aggressive correction. (sz, severe neuro abnormalities). Most likely to occur in acute setting such as: Post op menstruating females Exercise induced hyponatremia Hyponatremia associated with ecstasy Hyponatremia in patients with intracerebral pathology, Self induced water intoxication Symptomatic hyponatremia Aggressive correction at a rate of 1.52meq/L per hour for 3-4 hrs or until sxs resolve. Usually with hypertonic saline at 0.5ml/kg/hr However no more than 10-12meq/24hrs and 18meq/48hrs. Asymptomatic but <115 or 110 Such patient if they have sxs such as confusion, lethargy, gait disturbances will benefit from rise of 1meq/L/hr for 3-4 hrs but no faster than 8meq/24hrs. IF asymptomatic and >120meq/L then would benefit from free water restriction or treatment of volume depletion but no faster than 6-8meq/24hrs. Risk factors for Development of Osmotic demyelination Alcoholism Malnutrition Burns Severe Potassium depletion Elderly women on thiazide diuretics Urine flow= urinary solute excretion urinary osmolality Hypernatremia Causes of hypernatremia 1. 2. 3. 4. Inappropriately high water losses Insufficient water intake High Na intake without adequate water Thirst center/osmoreceptor lesion 4. Impaired thirst or osmoreceptors Causes usually tumor, granulomatous dz, ischemia, primary aldosteronism, age. Na>146 but not thirsty. Dilute urine after any H20 with impaired osmoreceptors 3. High NaCl intake without water Rare Seawater ingestion NaCl poisoning Hypertonic Na or bicarb boluses. 2. Insufficient water Intake Usually when ill or in the hospital setting Inadequate Free water Common after surgery, high nutrient intake, diuretics. 1. Inappropriately high water losses Sites of water loss 1. insensible (sweat, breath) 2. GI (vomitting, NG, Diarrhea) 3. Kidney DI Vasopressinase production Central (neurogenci) DI Nephrogenic DI Vasopressin (ADH) Receptors V2 Makes collecting duct permeable to water V1 Increases systemic BP Expressed in vasculature, liver and brain DI – lack of vasopressin Gestational DI Central DI Gestational DI 1 in 300,000 pregnancies Increased action of vasopressinase normally from the placenta Vasopressinase does not attack DDAVP as rapidly Central (neurogenic) DI Acquired- tumor, trauma, autoimmune, granulomatous, vascular Congenital- autosomal dominant Nephrogenic Congenital Acquired Drugs- LI, demeclocycline Hypercalcemia Hypokalemia Uretral obstruction Renal insufficiency Treatment Acute<24hrs Osmotic loss of brain water Accumulation of electrolytes: Na, K Chronic >24hrs Accumulation of organic solutes such as myo-inositol, sorbitol, others. Distribution of Total Body K+ Intracellular fluid: 3500meq (140meq/L) Muscle 2700meq Liver 250meq Erythrocytes 250meq Bone 300meq Extracellular Fluid 70meq (3.5-5meq/L) Normal Potassium Balance 100 mEq K+ RBC ~250 Muscle ~2500 Extracellular fluid 65 mEq Liver ~250 Bone ~300 90-95 mEq 5-10 mEq Regulation of K+ homeostasis 2 systems Intake/excretion Shifts between intracellular and extracellular Intake/output Avg american diet 100meq Potassium 90% Renal excretion. 10% GI Aldosterone stimulates GI excretion of K and in patients with renal failure this can be increased 4 fold. 6-12 hrs to excrete an acute load. Regulation of Renal Potassium Excretion 5 factors Aldosterone High distal sodium delivery High urine flow rate High K+ concentration in tubular cells Metabolic alkalosis Principal Cell Aldosterone Directly increases Na/K ATPase in the collecting duct cells leading to potassium secretion. Medical conditions that impair aldo pdxndiabetic nephropathy, CIN, ACEI, NSAIDS, heparin, spironolactone.. Conditions that increase aldo pdxn: primary hyperaldo, secondary due to diuretics, volume contraction… Distal Sodium delivery Diuretics such as thiazides, loop diuretics increase distal sodium delivery which then leads to increased distal sodium absorbtion and excretion of potassium Osmotic diuresis Luminal Flow rate Diuretics Osmotic diuresis Shifts Insulin Catecholamines Acid base Anabolism Shifts Epinephrine leads to stimulation of B2 adrenergic receptors which in turn stimulate the Na/K ATPase in skeletal muscle and lead to shift of K+ into the cells. Non selective B blockers block this effect. Lab evaluation of Potassium disorders Uk>20 suggests renal etiology. FEk normal 10%. Thus in hypokalemia it should be lower and higher in hyperkalemia. TTKG: (Uk/Pk)/Uosm/Posm Hypokalemia vs Potassium Deficiency Potassium deficiency can exist without hypokalemia and hypokalemia can exist without potassium deficiency DKA presenting with hyperK but is potassium deficient Patient with hyperthyroid periodic paralysis has hypok without deficiency HYPOKALEMIA <1% of individuals not taking meds develop hypokalemia Should always pursue workup Frequently occurs in the setting of diuretics, diarrhea, primary and secondary hyperaldosterone states. HYPOKALEMIA Ventricular arrhythmias esp<2.5 Muscle weakness, predispose to rhabdo by decreasing blood flow thru nitric oxide. Tetany, parasthesia Respiratory muscle weakness Polyuria- nephrogenic DI Increases renal ammonia production and worsens hepatic encephalopathy. ileus HYPOKALEMIA Pseudohypokalemia Cell shifts Inadquate intake GI loss Renal loss HYPOKALEMIA Uptake in metabolically active cells such as AML with marked leukocytosis Can prevent this lab finding by rapidly separating plasma cells or storing blood at 4deg celcius Cell Shifts Alkalosis- trivial effect Insulin B adrenergic activity- stress induced such as MI or drugs such as theophylline intox, ritodrine, terbutaline, albuterol Anabolism- TPN, treatment of prenicious anemia, rapidly growing leukemias Hypothermia Hypokalemic periodic paralysis Shifts Hypokalemic Periodic paralysis Intermittent acute attacks of muscle weakness with hypok triggered by large CHO meals, rest post exercise 2 forms- AD mutation in ca channel vs thyrotoxicosis in asian and mexican males 60meq K for acute attack and then d/c B blockers, correct hyperthyroid state HYPOKALEMIA Inadequate intake Unusual Kidney can lower K 5-15meq/day HYPOKALEMIA GI Loss Urinary K<20meq/L Diarrhea 30-50meq/L Vomitting- Kloss is due to renal loss as gastric juice has 5-10 meq/L but secondary hyperaldo and metabolic alkalosis HYPOKALEMIA Renal loss Urinary K> 20meq/L No history of diarrhea Divide into hypertensive vs. non Primary Mineralacorticoid Increase Incr R/A DDXMalignant HTN RAS Renin secreting tumor Primary Mineralacorticoid Increase Decr R/Incr A DDX- Conn’s syndrome Bilateral adrenal hyperplasia Gluc suppressible hyperaldo Glucocorticoid Suppressible Hyperaldo AD Chimeric gene formed by cross over of genetic material joining ACTH response element with coding region of aldo synthase Aldo secr from zona fasiculata Primary Mineralacorticoid Increase Decrease R and A DDX Cushings Liddle’s Syndrome of AME- 11 B OH steroid dehydrogenase def vs acquired def Activating mutation of mineralacorticoid receptor Liddle’s syndrome HTN, Metabolic alkalosis and hypokalemia. Nml-aldo negates a protein NED4 which would normally remove the sodium channel from the membrane. In Liddle’s there is a mutation in NED4 which leaves the sodium channel constitutively open. NO response to spironolactone but does respond to Triamterene Syndrome of Apparent Mineralacorticoid Excess Def of 11BOHSDehydrogena se Genetic acquired Genetic Causes of Hypok Alkalosis and HTN Activating mutation of mineralacorticoid receptor AD where the receptor is constitutively active. It is also activated by progesterone and pregnancy may make it worse. Increase in Sodium delivery Diuretics that act proximal to the cortical collecting duct Mg Def Bicarbonaturia-Acidosis- Prox and distal RTA Nonreabsorbed anions Bartters Syndrome Gitleman’s syndrome Increase Na Delivery Bartter’s – NMl bp, hypokalemia, metabolic alkalosis, high urine ca, low serum Mg sometimes. Impaired urine concentration Multiple Genetic defects can lead to this GItleman’s- Nml Bp, hypokalemia, metabolic alkalosis, low urine ca, normal urine concentration, low serum mg. One known genetic defect Primary Increase in Distal Na Delivery Failure to reabsorb Hco3, Ketoanions, PCN, Hippurate, salicylate obligates increase distal Na Delivery HYPERKALEMIA Pseudohyperkalemia Excess K intake Cell Shifts Impaired renal excretion- only cause of sustained hyperkalemia Hyperkalemia Mechanical trauma during venopuncture Familial pseudohyperkalemia- enhanced temprature dependent leakage of K out of rbc during venopuncture. Increase wbc and plt count Hyperkalemia Cell injury- rhabdomyolysis, tumor lysis, massive hemolysis, ischemia Toxins/drugs: digoxin, Chan su, tetrodotoxin, succinylcholine DKA, Nonketotic hyperosmolar state Hyperkalemic periodic paralysis Hyperkalemic Periodic Paralysis AD Mutation in skeletal muscle Na channel Episodic weakness precipitated by cold, ingestion of small amounts of potassium Hyperkalemia- shifts Mineral acidosis B blockade Increase tonicity Hyperkalemia- Impaired renal excretion Decrease in mineralacorticoid activity Decrease in distal Na delivery Abnormal cortical collecting duct Hyperkalemia Decrease in mineralacorticoid activity Adrenal insufficiency Drugs Hyperkalemia- Abnormal CCD Drugs- K sparing diuretics Tubulointerstitial nephritis Urinary obstruction Treatment of Acute Hyperkalemia 1) 2) 3) Assess urgency Stabilize myocardium: CaGluconate Redistribute K+ from ECF to ICF Ins/D50, Albuterol (high dose), NaHCO3, ?diur 4) Remove K+ from body Kayexalate, K loosing diuretics, dialysis Questions 27 yo dancer with serum K 3, HCO3 20. UNA 5, UK 7, UCL5 44 yo male with long h/o HTN, serum K 3, HCO3 30, UNA 30, UK 40, UCL40 with low renin and aldo ratio. Poor response to all bp meds except bp controlled with triamterene Questions 25 yo college student with serum K 3, HCO3 30, UNA 45, UK 45, Ucl 55. 21 yo asian male with h/o palpitations, tremors who upon waking up in the am could not move. Serum K 2. 45 yo male with metastaic cancer who presents with hypotension, hyperkalemia, hyponatremia. UK 5. FEK 5%, TTKG2 Questions 21 yo female medical student with serum K 3, HCO3 30, UNA 5, UK 40, UCL <10 44 yo male with CLL with wbc 70,000, K=7 without EKG changes Same patient undergoes chemotherapy and has K= 7 with EKG changes Answers 1. 2. 3. 4. 5. 6. 7. 8. Hypokalemic Periodic paralysis Tumor Lysis Hemolysis Diuretic abuse Laxative abuse Liddle’s syndrome Adrenal insuff Vomiting Clinical Presentation Patients may present with classic symptoms of renal colic and hematuria. Others may present with atypical sxs such as abdominal pain, nausea, difficulty urinating, penile pain or testicular pain. Asymptomatic nephrolithiasis may also be detected on imaging. Radiology Ultrasound Spiral CT – non contrast IVP KUB– calcium and cystine but not uric acid and MAP Calcium stones Calcium oxalate most common. Risk factors: low urine volume, male, obesity, high sodium intake, high animal intake with acidic urine (ethylene glycol) Calcium phos stones form in patients with RTA as low urinary citrate, hyperparathyroid patients as high urinary calcium and phos. Treatment Urine dilution First urine with sp grav <1.012 Volume >2.1 L /day Fluids at bed time Uric Acid Urolithiasis 5% of uric acid stones are due to secondary causes Radiolucent >800mg/dy in men and >750mg/dy in women Uric acid is less soluble than urate and at ph<5.5 only 100mg/l is soluble. Idiopathic Uric Acid Urolithiasis Men more often than women Usually over the age of 60 Often with gout Nml blood and urine concentration of uric acid Low Ph Tx with 4-6gm/dy of bicarbonate in divided doses. Moderate purine food intake. If still with hyperuricosuria then allopurinol. Infection Stones MAP, Struvite. Decreased incidence 3x higher in women than men Urea splitting by urease producing microorg Ph>8precipitation of MAP Proteus, corynebacterium, ureaplasma urealyticum, Serratia, Kleb pneum Infection Stone Radiopaque Rapidly enlarge, difficult to treat. May have an underlying calcium oxalate stone. Antibiotics, stone removal with percutaneous nephrolithotomy. Cystine Stone Autosomal recessive defect of transepithelial transport of dibasic aminoacids in the kidney and intestine. 1-2% of stones in adults but 10% in children 2nd-3rd decade of life but upto 7th decade 3L/dy of urine Alkalinize the urine to 7.5-8 Decrease methionine containing foods such as lobster, crayfish.. D penicillamine or tiopronin which cleave cystine. CYSTINE: Drug Induced stones 1% of stones Sulfadiazine in high doses can cause crystalluria. Protease inhibitors. Triamterene Genetic Diseases of the Kidney ADPKD Hypertension, Fh, multiple bilateral renal cysts. Liver, pancreatic cysts, diverticula, cerebral aneurysm, abd and thoracic aneurysms, MVP Renal failure by age 50. Genetic dz of Kidney Medullary Sponge Benign Hematuria, hypercalcuria, nephrocalcinosis, UTI IVP characteristic Genetic Diseases of the Kidney Alport’s X linked in 80% of patients. 10% AR Mutations in type IV collagen Hematuria, proteinuria. Hearing loss. Benign Familial Hematuria/Thin basement Hematuria but no esrd Genetic Dz of Kidney Fabry’s dz X linked Def in alpha galactosidase Proteinuria, neuropathy, angiokeratomas Progress to esrd. Check enzyme level. Renal bx Pregnancy Increase in GFR to 150ml/min Decrease in bicarb to 22 Decreased Na due to increase free water Increased baseline creatnine leads to complications during pregnancy, progression of renal dz and decreased fertility Pregnancy Preeclampsia BP>140/90, proteinuria usually after 20 weeks gestation, edema, neurologic sxs, Nullliparous women, renal dz, htn, obesity, dm, extremes of age, multiple gestations. Increased uric acid. Tx bp, mg, deliver Pregnancy HELLP TTP HUS Chronic HTN Gestational HTN mid pregnancy but no proteinuria GN Nephrotic syndrome- Edema, proteinuria >3.5gm/day, hyperlipidemia, hypercoag Bland urine sediment Nephritic syndrome: HTN, RI, active urine sediment. GN- Nephrotic Minimal change Dz: Sudden onset Heavy proteinuria Young (<30) Secondary causes: Hodgkins, Li, NSAIDs Tx Steroids upto 16 weeks. 1mg/kg GN- Nephrotic FSGS AA, bland sediment . Progresses to ESRD. Secondary causes: HIV, Obesity, Solitary kidney, heroin use, reflux nephropathy Usually slow progressive. Ace and arbs GN- Nephrotic Membranous Usually age >50 Secondary casues: solid tumors- lung, breast, colon. SLE class 5, Hep B 1/3 progress, 1/3 resolve and 1/3 stable. Cytoxan and prednisone GN- Nephrotic Diabetes- hyperfiltration, microalb, nephrotic. Bp, glucose control and ace/arb Amyloidosis- primary (malignancy) vs secondary from chronic inflammatory state. Albuminuria, orthostatic hypotension, liver abnml, cardiomyopathy. GN- Nephrotic Multiple myeloma AKI- hypercalcemia Light chains obstructing kidney LCDD Albuminuria vs proteinuria. Nephritic dz- Anti GBM 0.5/1,000,000 per yr in caucasians 10-20% of cases RPGN Mediated by antibodies to type IV collagen found in GBM Type IV collagen is also found in the lungs Lung involvement more common in young men Goodpasture’s dz Nephritic dz- Anti GBM Can rapidly progress to widespread crescent formation Most common cause of death is pulmonary hemorrhage in early disease Pathology shows focal segmental glomerulonephritis diffuse proliferative GN with extensive crescent formation Immunofluorescence shows linear ribbon-like deposition of IgG along the GBM http://jeffline.tju.edu/Education/dl/NU570/cases/images/CASE8B-1.JPG http://pathmicro.med.sc.edu/ghaffar/goodpasture.jpg Nephritic dz- Pauci immune GN Incidence of 2/100,000 per year Peak in 60s with ♂=♀ Constitutional sx: lethargy, malaise, anorexia, weight loss, fever, arthralgias, and myalgias ANCA+, normal C3C4, ↑ESR, leukocytosis, NCNC anemia, Nephritic dz- Pauci immune GN Wegener’s granulomatosis Small vessel vasculitis Smoldering GN to RPGN in 77% of pts Dominated by respiratory manifestations such as sinusitis, nasal cartilage collapse, cavitating lung lesions Serology + for c-ANCA Bx: focal progreesing to diffuse proliferative GN, granulomas are rarely seen on kidney bx Nephritic dz- Pauci immune GN Microscopic polyangiitis Mean age of onset 57 yrs men>women Also a small vessel vasculitis Systemic dz involving lungs, GI and skin vasculitis GN in 79% of pts Immunofluroescence in both wegener’sand microscopic polyangiitis shows paucity of immune deposits Immune complex GN GN associated with a variety of infections Poststreptoccoccal GN Endocarditis HCV HBV Poststreptoccoccal GN Most commonly in children 2-6 years old Caused by infxn with nephritogenic strains of group A strep Occurs about 2 weeks days after pharyngitis or impetigo Pts present with oliguric ARF Poststreptoccoccal GN Low C3, normal C4 >90% of pts have Abs to streptococcal antigens such antistreptolysin O (ASO) Renal lesion is typically a diffuse proliferative GN Immunofluorescence typically show a granular pattern Crescents are uncommon http://www.med.niigata-u.ac.jp/npa/Lectures/Images/Slides/PSGN/2PSAGN_L.gif http://cnserver0.nkf.med.ualberta.ca/cn/Schrier/Vol2/f3442-2.jpg Lupus nephritis 40 to 85% of pts with SLE have renal involvement Mild urinary findings to CRF with nephritic or nephrotic syndrome ANA found in 95-99% of SLE pt though nonspecific Anti ds DNA is highly specific for SLE, titers correlate with level of lupus nephritis Lupus nephritis 5 classes of renal lesions in SLE Class Class Class Class Class I normal kidney Do not present with II mesangial proliferation acute nephritis III focal prolifertive GN IV diffuse proliferative GN V membranous nephropathy Correlation between clinical features and dz activity is poor, bx is important in guiding tx GN- Nephritic IGA nephropathy Hematuria. Most common 1/3 synpharyngitic 1/3 proteinuria 1/3 progress to ESRD HSP Cresentic IGA Ace plus arb, steroid Secondary: HSP, chronic liver dz, HIV GN- Nephritic RPGN- 3 types 1. Ab mediated against basement membrane. Anti GBM dz 2. Ag-Ab complex deposit in the GBM: SLE, HepC, post strep, post infectious, endocarditis associated, IGA 3. Pauci immune: Wegner’s, Microscopic polyangiitis, Churg strauss Acute Glomerulonephritis Proteinuria and hematuria. Quantify the proteinuria. Acitve urinary sediment with dysmorphic red blood cells or rbc casts. Low complements in SLE, MPGN, post strep or endocarditis or infections. ANCA and Anti GBM titers. ANA SLE Active serologies: low complements, pos ana, anti double stranded DNA Proteinuria and Hematuria Must bx Treat class 3,4 (maybe5) with cytoxan/ pred vs mycophenolate. Pulmonary Renal syndrome CHurg strauss Wegner’s- anti proteinase 3 Goodpatures- anti gbm ab. MPA- anti myeloperoxidase SLE cryoglobulinemia Renal Replacement Modalities IHD PD CRRT Transplant