Renal
Andrew J. Klein, M.D.
Chi-yuan Hsu, M.D., M.Sc.
Acute reversible renal dysfunction
Continuous renal replacement therapy
Drugs requiring adjustment in renal failure
1. What is acute reversible renal dysfunction? ARRD is a new term for acute renal failure (ARF). It is defined as a sudden decrease in renal function, resulting in an inability to maintain fluid and electrolyte balance and to excrete nitrogenous wastes. In terms of numbers: a 50% increase or greater in serum creatinine above baseline or reduction in creatinine clearance by 50% or more.
2. Symptoms: often nonspecific, including nausea, vomiting, abdominal pain, altered mental status, and bleeding (platelet dysfunction).
3. Physical exam: Important findings to look for are a pericardial friction rub, muffled heart sounds with increased JVP from the effusion secondary to uremic pericarditis, crackles secondaryto volume overload, decreased bowel sounds from ileus, asterixis and confusion.
4. Etiology:
· Prerenal causes: common and can progress to ATN if severe and prolonged
- Hypovolemia: vomiting, diarrhea, diuretics, hemorrhage, osmotic diuresis (diabetes melliuts, DKA, hypercalcemia), burns, Addisonian crisis.
- Decreased effective intravascular volume: CHF, cirrhosis, nephrosis, shock.
- Commonly precipitated by renal vascular changes: ACE-I, cyclosporine, NSAIDs.
· Postrenal causes:
- Ureteric: bilateral calculi, blood clot, cancer, external compression (retroperitoneal fibrosis).
- Bladder neck: neurogenic bladder, spinal cord injury, prostatic hypertrophy, calculi, cancer, blood clot, anticholinergic drugs.
- Urethral: stricture, congenital valve.
- Intratubular obstruction: various crystals (uric acid, calcium oxalate, acyclovir, crixivan).
· Intrinsic renal causes: classified according to site of injury
- Acute tubular necrosis (ATN): most common intrinsic renal cause among hospitalized patients. Main risk factors of ATN:
• Ischemic: any prolonged prerenal or hypotensive state; vascular obstruction such as renal artery occlusion.
• Toxic: aminoglycosides, amphotericin, rhabdomyolysis, hemolysis (radiocontrast dye can lead to ATN but also causes “contrast nephropathy”, a distinct entity).
• Sepsis physiology (even without hypotension).
- Acute interstitial nephritis (AIN):. Classic triad includes fever , rash and eosinophilia.
• Allergic (most common): penicillins, cephalosporins, sulfas, NSAIDs, rifampin, many other rare causes
• Infections: leptospirosis, hantavirus, streptococcal, CMV, histoplasmosis, Rocky Mountain spotted fever.
• Autoimmune disorders: some cases of SLE, Sjogren’s disease.
- Glomerulonephritis (GN): see Renal: Acute Glomerulonephritis.
5. Diagnostic evaluation:
· History: NSAIDs, diuretics, BPH, stones, cancer, anticholinergic drugs.
· Place Foley to relieve obstruction—especially if anuric; check post-void residual and if Foley already present, flush to rule out obstructed catheter.
· Check BUN/Cr ratio: > 20/1 implies prerenal (beware other causes of increased BUN).
· Calculate FENa [(UNa/PNa / UCr /PCr) x 100] only if the patient is oliguric (< 400mL/24h): <1% favors prerenal, >1% favors intrarenal or ATN (decreased concentrating capacity). The FENa is not helpful if the patient is not oliguric.
· Examine the urine:
- Prerenal: bland, hyaline casts; postrenal: normal or red cells, white cells, or crystals.
- ATN: muddy brown casts, granular casts.
- AIN: WBCs (not that specific); WBC casts, eosinophils (both specific but insensitive). WBCs with negative leukocyte esterase reaction can be a clue for eosinophiluria.
- GN: dysmorphic RBCs, RBC casts (also specific but insensitive).
- Proteinuria: raises suspicion for GN (especially if nephrotic-range (>3gm/24h) or in combination with hematuria). < 1-2 g/24hr often seen in AIN.
· Check urine chloride if metabolic alkalosis present (causes a falsely high urine sodium).
· Check CK if concern for rhabdomyolysis; ATN usually seen only when CK > 6000.
· Spot urine for protein/creatinine ratio as an estimate of protein, 24 hr urine protein if present.
· Obtain renal ultrasound to look for:
- Hydronephrosis (obstruction): sometimes can be seen with retroperitoneal fibrosis secondary to radiation/cancer and there may not be urinary tract dilation—image with CT or MRI.
- Asymmetric kidney size: seen in renal artery stenosis.
- Bilateral small kidneys: seen in chronic renal disease; biopsy is of little yield in these patients
- Large kidneys: seen in diabetes mellitus, amyloid, PCKD, HIV).
· Observe urine output: oliguric (<400mL/24h) renal failure is associated with worse prognosis, except with contrast nephropathy (typically oliguric with good recovery).
6. Treatment: Specific treatments depend on etiology. Some possibilities:
· Prerenal: fluid challenge with small boluses, avoid nephrotoxic drugs.
· Postrenal: catheterization, distinguish post-obstructive diuresis from appropriate excretion of salt and water accumulated during ARRD; monitor K+.
· Renal: consult renal
- Discontinue contributing drugs (NSAIDs, nephrotoxins).
- For rhabdomyolysis or acute uric acid nephropathy, give D5W + 3 amps NaHCO3/L at 100-150 ml/hr, titrate to high volume UOP with urine pH > 6 (note: in established cases with oliguria, excessive volume may be detrimental).
· In general:
- Manage fluids carefully, especially if oliguric – watch for pulmonary edema.
- Watch electrolytes, especially K, Mg, HCO3, PO4, and Ca++ (be careful with IV calcium in hyperphosphatemia – Ca x PO4 products >70 can cause metastatic calcification).
- Renally dose all medications.
- Treat bleeding with PRBC (hematocrit > 30 has better outcome in uremic bleeding), DDAVP (0.3mcg/kg – note: rapid tachyphalaxis), estrogens, or hemodialysis (best therapy).
· Data is accumulating that aggressive dialysis (i.e., earlier start, more frequent, more intense) may decrease morbidity and mortality.
1. Clinical characteristics:
2. Risk factors:
3. Prophylaxis:
- The initial study on acetylcysteine was done in stable outpatients with chronic renal insufficiency and not in hospitalized patients. There has also been conflicting data regarding acetylcysteine’s use in cardiac catheterization patients. However, because of its low risk profile, it should be given as prophylaxis in all patients that have the above risk factors.
- Acetylcysteine is probably not a “wonder drug” for the prevention of contrast nephropathy. Therefore, continue to use your clinical judgment in weighing the risks and benefits of obtaining a contrast study in your patient that is a risk for contrast nephropathy. Your patient is probably still at the same risk for contrast nephropathy, regardless of whether you use acetylcysteine or not.
· Fenoldopam: there is some data to suggest that fenoldopam (a selective dopamine-1 (DA-1) receptor agonist) may have use in the prevention of contrast nephropathy. A large-scale randomized trial studying fenoldopam’s use in preventing contrast nephropathy is currently ongoing. Consider its use in very high risk patients and those patients with the above risk factors who are undergoing cardiac catheterization.
- Protocol: start the infusion 15-30 minutes prior to the contrast study at a dose of 0.03 mcg/kg/minute to a maximum of 1.0 mcg/kg/minute. Titrate up the dose to keep the systolic BP at least 90 mmHg (fenoldopam can cause hypotension). Continue the infusion for 6 hours after the contrast study is completed.
4. Treatment isgenerally supportive. In most cases, the reduction in renal function (seen at 24-48 hours after contrast is given) resolves within 1 week. However, if the patient progresses to full blown renal failure, the only known treatment is initiation of hemodialysis. In cases like these, consult renal.
1. Clinical clues: relatively acute onset of hematuria, oliguria, acute renal failure if secondary to RPGN; time course depends on disease and ranges from days to weeks (anti-GBM) or weeks to months (lupus, ANCA).
2. Physical exam: extracellular volume expansion, edema, hypertension secondary to impaired GFR, decreased excretion of salt and water.
3. Urinalysis: RBC casts, dysmorphic red cells, leukocytes, sub-nephrotic-range proteinuria, microscopic hematuria.
4. Diagnosis: Renal biopsy is the gold standard, although serologic markers such as ANCA may obviate the need for biopsy.
5. Treatment: Rapid diagnosis and prompt therapy critical to avoid irreversible renal failure. Inflammatory disorders are treated with steroids ± cytotoxic agent (consult renal). If secondary to systemic disease, you must also treat underlying disorder .
|
Category |
anti-GBM |
pauci-immune glomerulonephritis |
immune complex glomerulonephritis |
mimickers |
|
Serologic markers |
anti-GBM antibody |
ANCA+ (anti-PR3 or anti-MPO) |
low C3/C4 |
anti-GBM (-), ANCA (-), Normal C3 |
|
Differential Diagnosis |
anti-GBM disease, Goodpasture’s syndrome |
Wegener’s, Churg-Strauss, microscopic polyarteritis nodosa, renal-limited crescentic GN |
MPGN, post-infectious GN (ASO+), lupus nephritis (ANA, anti-dsDNA+), cryoglobulinemia (cryo+, HCV±), SBE, shunt nephritis, IgA nephritis/HSP (usually normal complements) |
malignant hypertension, HUS/TTP, interstitial nephritis, scleroderma, atheroemboli, cast nephropathy in multiple myeloma |
1. Pathophysiology: due to increased glomerular permeability to serum proteins.
2. Causes: can be differentiated either by primary renal disease and corresponding renal pathology or underlying condition (in secondary causes of nephrotic syndrome):
· Primary renal disease:
- Minimal change disease: primary form most commonly seen in children, responsive to steroid therapy, usually does not progress to ESRD; secondary form associated with lymphoma, NSAIDs
- Focal glomerulosclerosis (FSGS): There is a primary form that is probably an autoimmune disease in the same spectrum but more severe than minimal change disease. Similar pathological changes can be seen in association with heroin, HIV, NSAIDs. There are also secondary forms that are found in clinical situations where there is “mismatch” between nephron number and “renal work” (e.g., in obese patients; or after nephron loss from other cause such as GU reflux or prior GN). Leading hypothesis holds that this FSGS is secondary to compensatory glomerular hyperfiltration. Decreased renal function and HTN common. If primary, treat with steroids ± cytotoxic agents. If secondary, treatment is conservative (ACE-inhibitor, etc). Often progresses to ESRD.
- Membranous glomerulonephritis: common in adults, associated with cancer, hepatitis B, SLE. Treat with steroids ± cytotoxic agents.
- Membranoproliferative glomerulonephritis: type I – low C3, associated with hepatitis C, cryoglobulins; type II – C3 nephritic factor (+), mostly pediatric.
· Secondary causes: the following is only a partial listing:
- Tumor (e.g. lymphoma, multiple myeloma).
- Heroin and other toxins (e.g. gold).
- Infectious (e.g. hepatitis B and C, HIV, syphilis).
- Systemic (e.g. SLE, amyloid, diabetes).
3. Clinical findings: urine protein excretion > 3.5 g in 24 hours, hypoalbuminemia (< 3.0 g/dl), hyperlipidemia (fasting total cholesterol > 200 mg/dl), edema/anasarca, hypercoagulability (loss of native anticoagulants antithrombin III, protein C and S).
4. Diagnosis: primarily by renal biopsy although ancillary laboratory testing can give clues. Also, large kidneys on ultrasound favor diabetes, HIV, or amyloidosis.
5. Therapy is cause specific with the addition of: diuretics, salt restriction, ACE-inhibitor, rigorous blood pressure control lowering, and lipid-lowering agents. Consider anticoagulation mainly in membranous nephropathy (highest risk of thrombosis, especially renal vein thrombosis).
6. Complications: include infections, thrombosis, atherosclerosis, and wasting.
Orth SR,
Ritz E. The nephrotic syndrome. N Engl J Med. 1998 Apr 23;338(17):1202-11.
1. Specific gravity: useful in indicating effective circulating volume; rule of thumb is that specific gravity of 1.010 (iso-osmotic) does not correlate with urine osmolality when large particles such as contrast media are present in the urine.
2. Urine pH: normally 4.5-8, alkaline (> 7) with urea splitting organisms such as Proteus (usually not e. coli) infection, metabolic alkalosis; acidic (< 5) with metabolic acidosis, with urolithiasis suggests uric acid stone (or nidus).
3. Leukocyte esterase: screens for >10 WBC/hpf, false positive with interstitial nephritis, vaginal contaminant. False negative with high specific gravity, glucosuria.
4. Nitrites: produced by gram negative bacteria (converts nitrates to nitrites); misses enterococcus (gram positive). In order for bacteria to convert dietary nitrates to nitrites, urine must incubate in the bladder for > 4 hours.
5. Blood: free hemoglobin produces a homogenous color, intact red cells produce punctate staining; can also be positive with myoglobinemia. Dipstick positive for blood and no RBC’s on microscopy is a clue that rhabdomyolysis (myoglobin) or hemolysis (hemoglobin) may be occurring.
6. Ketones: seen in DKA, alcoholic ketoacidosis, starvation. Misses acetone and b-hydroxybutyrate. False positive with levodopa metobolites.
7. Bilirubin/urobilinogen: usually only conjugated (water soluble) bilirubin is found in urine; however, when serum bilirubin is high, unconjugated bilirubin (usually bound to albumin) can be detected. Conditions associated with high levels of bilirubin also result in the appearance of urobilinogen in the urine, unless there is biliary obstruction.
8. Protein: 1+ ~ 30 mg/dl, 2+ ~ 100 mg/dl, 3+ ~ 300 mg/dl, 4+ ~ > 2000 mg/dl. Not a sensitive test for microalbuminuria and misses Bence-Jones proteins.
9. Glucose: seen when serum glucose > 180 mg/dl (the level at which the proximal tubule reabsorptive capacity for glucose is exceeded).
10. Microscopy:
· Dysmorphic RBCs, RBC casts: glomerulonephritis.
· WBC casts: pyelonephritis, interstitial nephritis.
· Muddy brown casts: ATN.
· Crystalluria: uric acid, ethylene glycol intoxication, drug-induced (sulfa, acylovir, indinavir).
· Hyaline/granular: pre-renal, non-specific.
1. Facts:
· Affects men greater than women 4:1, initial presentation in 3rd and 4th decade.
· Main types: calcium oxalate, calcium phosphate, struvite, uric acid, and cystine.
· 70% composed of calcium and therefore radio-opaque.
2. Clinical presentation and diagnosis:
· Sudden onset colicky, flank pain that radiates, described as worst pain ever experienced. Stone location:
- At uretopelvic junction: flank pain predominates.
- At crossing of iliac vessels: radiates to genitalia.
- At uretovesicular junction: voiding symptoms, radiates to genitalia.
- At bladder neck: anuria, suprapubic pain.
· Associated nausea and vomiting.
· Patient constantly moving trying to find comfortable position.
· Size of stone does not correlate with symptoms.
· Hematuria, normal to slightly increased WBC.
· Imaging gold standard: abd/pelvic CT with stone protocol.
3. Therapy:
· 98% stones < 5 mm pass spontaneously. However stones >7-8 mm have < 20% chance of passage.
· If associated UTI, urosepsis, persistent obstruction, intractable pain, nausea, or vomiting – requires intervention, hospitalization for ureteroscopic stone extraction or extracorporeal shock wave lithotripsy (ESWL).
· Pain relief with NSAIDs, opiates.
· Drainage and antibiotics if evidence of infection.
· Volume repletion if intractable nausea or vomiting or electrolyte derangements; not helpful for stone passage.
· Strain urine for stone analysis.
· Increase fluid intake and metabolic work-up (e.g., evaluate for hypercalcuria) to prevent recurrence.
· Prevention of reoccurrence depends upon type.
Manthey DE, Teichman J. Nephrolithiasis. Emerg Med Clin North Am. 2001 Aug;19(3):633-54
1. Causes:
· Coliforms in community-acquired uncomplicated UTI infection – E. Coli (80%), Staph. saprophyticus, Klebsiella, Proteus.
· Acute infection is usually caused by a single pathogen.
· Predisposing factors: female (short urethra), sexual intercourse, diaphragm-spermicide use, uncircumcised men, BPH.
2. Symptoms and signs:
· Irritative voiding symptoms (frequency, urgency, dysuria).
· Suprapubic tenderness (cystitis).
· Costovertebral angle tenderness, fever (pyelonephritis).
· Hypotension (urosepsis), altered mental status (urosepsis).
3. Differential diagnosis:
· Vulvovaginitis, pelvic inflammatory disease, prostatitis, urethritis (abnormal discharge, new partner), stone disease, cancer, chemotherapy (cyclophosphamide), interstitial cystitis.
4. Workup:
· Urinalysis: increased pH with Proteus; leukocyte esterase (+), nitrite (+) (unless gram positive), ± hematuria, > 5 WBC/hpf, ± WBC casts (pyelonephritis).
· Urine culture: gram stain, urine culture. Diagnosis is usually made on clinical grounds alone. However, urine culture can be helpful to document pathogen in resistant or recurrent cases. In asymptomatic UTI, make diagnosis with > 100,000 colonies/mL. In symptomatic UTI, as low as 1000 colonies/mL can be considered abnormal. If the patient has sterile pyuria – consider TB, interstitial nephritis, or partially treated UTI.
· Ultrasound or CT: obtain only if patient is systemically very ill or remains persistently hypotensive or febrile—rule out obstruction, stone, cysts, or abscess.
5. Classification and therapy:
· Uncomplicated cystits: (no symptoms of pyelonephritis): fluoroquinolone or TMP/SMX (high resistance in some areas) or augmentin (if pregnant) x 3 days. Women need a pelvic exam if they have risk factors for STD. Men need further evaluation if no obvious risk factors present.
· Uncomplicated pyelonephritis:
- Outpatient: fluoroquinolone x 7 days, TMP/SMX or Augmentin x 14 days.
- Inpatient: admit to hospital if the patient is pregnant, elderly, diabetic, has intractable nausea/vomiting (can’t take PO’s), or has signs of urosepsis. Treatment consists of a fluoroquinolone, ampicillin/gentamycin, or ceftriaxone (misses enterococci) x 14 days.
· Unresolved infection (same species isolated): consider resistance, noncompliance, infected stones, prostatitis, fistula, or obstruction.
· Recurrent infection (> 3 episodes per year): eradicate infection completely (as evidenced by urine culture). Then treat with daily TMP/SMX.
· Complicated UTI (anatomic, functional abnormalities, reflux, obstruction, transplant, Foley-related): beware of Pseudomonas, Candida. Correct underlying problem.
1. Assure yourself that the renal insufficiency is indeed chronic through review of time course of rise in creatinine; anemia favors chronic (rather than acute renal insufficiency).
2. Causes: most commonly associated with diabetes and hypertension. Followed by glomerulonephritis and polycystic kidney disease (PCKD).
3. Ultrasound usually shows echogenic, small kidneys bilaterally (some exceptions are diabetes, myeloma, HIV, amyloid, PCKD).
4. Tips: keep the following in mind for your renal patients:
· Anemic typically when renal function < 30%: normocytic, low reticulocyte count (hematocrit usually 22-30%). Secondary to low erythropoietin, blood loss.
· Avoid NSAIDs, metformin, contrast, and most oral sulfonylureas.
· If bleeding diathesis is present, treat with blood transfusion, dialysis, DDAVP, estrogens, and erythropoietin.
· Renal diet and low protein diet: don’t use them. These patients need nutrition and you have dialysis to manage things like potassium.
· Nephrocaps 1 po qd to replace water-soluble vitamins lost in hemodialysis.
· Calcium binders (see hyperphosphatemia section).
· Renally adjust all medications (your friendly pharmacist can help).
· Avoid magnesium containing compounds such as MOM and Mylanta. Also avoid phosphorous containing compounds such as a Fleets enema.
· Be careful with maintenance IVF – ESRD patients may not need any.
· On exam, check access sites: catheters without infection, thrill over shunt? (2 kinds: native AV fistula and PFTE grafts).
· Do not use current or potential upper extremity shunt sites for blood draws and/or IVs.
· Do not take BP in extremity with a shunt.
· Avoid PICC lines (increased risk of central vein stenosis therefore jeopardizing future shunt site/function).
Parmar MS. Chronic renal disease. BMJ. 2002 Jul 13;325(7355):85-90.
The mnemonic “AEIOU” is often taught for indications for emergent dialysis. Note that there is increasing data to suggest benefit with early initiation of dialysis prior to the occurrence of these “absolute” indications in both the acute and chronic settings.
· Acidosis, especially if severe (pH < 7.2 and refractory to HCO3 or unable to give HCO3 due to volume overload).
· Electrolytes, especially potassium > 6.5-7 mmol/L or with ECG changes. Temporize with calcium, D50 + insulin, HCO3, beta-agonist nebulizers, and kayexalate.
· Ingestions, especially those that cause renal failure such as lithium or ethylene glycol.
· Overload, i.e. volume overload causing pulmonary edema. Temporize with nitrates and large doses of furosemide (160–200 mg IV).
· Uremia, i.e. confusion, pericarditis, seizures, platelet dysfunction with severe bleeding, and intractable nausea/vomiting.
1. Uses peritoneum as the dialysis membrane:
· Continuous ambulatory PD (CAPD): 2-3 liters abdominal dialysate with changes 4-5x/day.
· Continuous cycling PD (CCPD): automated exchanges during sleep, may use CAPD in addition.
· CCPD requires a special machine-when patients who do CCPD are admitted to the hospital. Obtain a renal consult for these patients.
2. Fluid removal is controlled by concentration of dialysate (1.5%, 2.5%, 4.25% glucose) and frequency of exchanges (max fluid removal with 4.25% q1h).
3. Complications:
· Peritonitis: usually managed as outpatient with intraperitoneal antibiotics. Send fluid for STAT cell count, differential, Gram stain, and cultures. Because solutions are glucose containing, the cut-off for peritonitis is low: > 50 PMNs/mm3 is peritonitis. Antibiotics are based on gram stain: if gram stain is negative cover for both gram positive cocci and gram negative rods. Common infections: staph epi (30-45%), staph aureus (10-20%), strep (5-10%), coliforms (5-10%), klebsiella/enterobacter (5-10%). Antibiotics should be given for at least 2 weeks. Admit for recurrent infection, failure to respond to appropriate antibiotics, abscess, pain control, etc. Polymicrobial peritonitis especially with gram negative or anerobes should prompt work-up for perforation.
· Refractory peritonitis, tunnel infection: may need to remove peritoneal dialysis catheter.
· Hyperglycemia: can use escalating doses of SQ NPH or intraperitoneal insulin.
Vargemezis V, Thodis E. Prevention and management of peritonitis and exit-site infection in patients on continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant. 2001;16 Suppl 6:106-8.
Oreopoulos DG. Pathogenesis and management of complications of chronic peritoneal dialysis. Nephrol Dial Transplant. 2001;16 Suppl 6:103-5.369-75.
1. Two slightly different modalities are frequently used: continuous venovenous hemofiltration (CVVH) and hemodiafiltration (CVVDF).
2. Used primarily in patients who cannot tolerate conventional hemodialysis due to hypotension.
3. Good for removing large volumes of fluid since it is a continuous modality of therapy. Fluid removal is on a cc/hour basis (typical starting point is 50-100 cc/hour, versus the 1000 cc/hour removed with conventional hemodialysis). With hypotension, patients are frequently run “net even” so that fluid balance is matched. Since fluid control is entire controlled by CVVHD, close collaboration with the renal consult team is needed to prevent miscommunication (e.g., blood product or IVF at 200 cc/hour to improve hypotension in a patient “running even” will be promptly removed by CVVHD the next hour unless otherwise specified).
4. CRRT is slower than conventional hemodialysis for acute solute removal (toxin overdose, severe hyperkalemia).
5. Requires ICU care.
6. Drug clearances are typically higher than conventional thrice-weekly hemodialysis.
7. The renal consultant is in charge of all orders for electrolyte repletion when the patient is on CRRT.
1. Remember to always call pharmacy if in doubt.
2. Antibiotics: always check the Sanford Guide to Antimicrobial Therapy or similar resource.
3. Consider changing atenolol to metoprolol.
4. Avoid metformin and most oral sulfonylureas.
5. Other common medications that require dose adjustment:
· H2 blockers
· Allopurinol
· Digoxin
· Lithium