Approach
Your Organizational Guidance
ebpracticenet urges you to prioritize the following organizational guidance:
Chronisch nierlijden (multidisciplinaire aanpak)Published by: WORELLast published: 2017GPC pluridisciplinaire sur la néphropathie chronique (IRC)Published by: Groupe de travail Développement de recommandations de première ligneLast published: 2017The timing of investigations depends on the clinical condition of the patient and the rate and magnitude of change in serum creatinine.
In asymptomatic or mildly symptomatic patients, elevations in serum creatinine can be systematically evaluated. However, in severely ill patients with multiorgan involvement, an early renal biopsy should be considered to expedite diagnosis and treatment.
If there is evidence of fluid overload or uremic signs and symptoms, treatment should be instigated in parallel with urgent investigations.
Initial assessment
Current serum creatinine values should be compared with previous serum creatinine values, if available, to distinguish acute from chronic changes. If previous values are not available, all values outside of the reference range should be treated as acute changes.
The Acute Kidney Injury Network criteria determine whether patients meet the criteria for acute kidney injury (AKI):[45]
Absolute increase in serum creatinine of ≥0.3 mg/dL (≥26.4 micromol/L), or
Percentage increase in serum creatinine of ≥50% (1.5-fold from baseline), or
Reduction in urine output (documented oliguria of <0.5 mL/kg per hour for >6 hours).
If the elevation in serum creatinine is acute, the magnitude and rate of rise in serum creatinine should be determined, as this provides clues as to the underlying cause and guides appropriate management:
The typical rise in serum creatinine in AKI is 1 to 2 mg/dL/day (88 to 177 micromol/L/day).
Serum creatinine rises >1 to 2 mg/dL/day (>88 to 177 micromol/L/day) should prompt suspicion of rapidly progressive glomerulonephritis or rhabdomyolysis. Rises as high as 5 mg/dL/day (442 micromol/L/day) may be seen in rhabdomyolysis.
An acute increase in serum creatinine against the background of chronic kidney disease (CKD) may indicate progression of the underlying condition. However, other causes of elevated serum creatinine should be excluded first. Fluid balance issues, medications, contrast exposure, and worsening of comorbid conditions are the most common causes and may be reversible.
History
Most of the underlying causes produce few or no specific symptoms. Assessment of current symptoms should include enquiry about symptoms of uremia.
Current symptoms
Symptoms of uremia are often vague. They include nausea, vomiting, fatigue, reduced appetite, muscle cramps, pruritus, and altered mental status. Uremia usually occurs in advanced AKI or in advanced CKD.
A history of trauma, severe vomiting, or diarrhea should prompt suspicion of volume depletion.
Joint pain, rash, progressive shortness of breath, hemoptysis, persistent sinusitis or otitis, scleritis or paresthesia should prompt suspicion of vasculitis.[86]
Fever and sore throat should prompt suspicion of streptococcal infection (causing glomerulonephritis).
Jaundice should prompt suspicion of hepatitis B or C infection, or hepatorenal syndrome.
Shortness of breath with peripheral edema may indicate heart failure.
Weight loss should prompt suspicion of an underlying malignancy.
Obstructive (voiding) and irritative (storage) symptoms should prompt suspicion of obstructive uropathy.
Severe loin pain with frank hematuria should prompt suspicion of acute renal infarction or nephrolithiasis.
A history of polyuria, polydipsia, polyphagia, weakness, and/or weight loss should prompt suspicion of diabetic ketoacidosis.
Pregnancy should prompt suspicion of preeclampsia or exacerbation of underlying kidney disease.
Past medical history
Chronic renal failure.
Previous acute renal failure.
Other underlying conditions that may cause raised serum creatinine include hypertension (hypertensive nephropathy), diabetes (diabetic nephropathy), autoimmune diseases (vasculitis), cirrhosis (hepatorenal syndrome), lymphoproliferative disorders (cryoglobulinemia), paraproteinemias, and infections (postinfectious glomerulonephritis, cryoglobulinemia).
Surgical history
Recent surgery may indicate hypovolemia, renal ischemia (due to clamping of arteries during cardiac surgery), or renal transplant rejection.
Multiple cholesterol emboli syndrome can occur following arterial manipulation, vascular surgery, stent placement, or cardiac catheterization.
A small rise in serum creatinine following kidney donation or unilateral or partial nephrectomy is expected and should resolve.
Drug history
A thorough drug history is important, as the range of drugs known to cause elevated serum creatinine is extremely wide.
Cimetidine, gentamicin, fibric acid derivatives other than gemfibrozil, and trimethoprim inhibit creatinine secretion.
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers increase serum creatinine levels by 20% to 30% due to prerenal effects.[68]
Penicillamine, gold sodium thiomalate, nonsteroidal anti-inflammatory drugs (NSAIDs), captopril, mitomycin C, and cyclosporine can cause glomerulonephritis, as can heroin.
Many medications are known to cause acute interstitial nephritis.
Aminoglycosides, amphotericin-B, chemotherapeutic agents (e.g., cisplatin), NSAIDs, and radiocontrast media can cause acute tubular necrosis.
Some patients have an increase in serum creatinine within a few months after starting fenofibrate, an entity known as fenofibrate-associated creatinine increase.[87]
Nutrition history
Creatine is often taken as a supplement to boost muscle mass and increase athletic performance. Prolonged intake of creatine supplementation of >10 g/day may increase serum creatinine concentrations, but is unlikely to affect estimates of creatinine clearance.[62][63] The serum creatinine levels should return to baseline values upon discontinuing supplemental creatine.
A vegetarian diet is associated with decreased generation of creatinine, and ingestion of cooked meat causes a transient increase in serum creatinine.
Examination
The examination may be unremarkable in many patients, but is most useful to differentiate systemically ill patients (who require immediate treatment and early renal biopsy) from other patients who can be investigated systematically.
Patients with shock appear ill, with decreased blood pressure, increase in heart rate, and increased respiratory rate with a possible decrease in oxygen saturations or reduced level of consciousness.
Uremic signs such as asterixis or altered mental status, and/or signs of fluid overload (e.g., pulmonary or peripheral edema), indicate severe renal failure requiring immediate treatment. Early renal biopsy to establish the cause should be considered in these patients.
The presence of rash should prompt suspicion of vasculitis or a microangiopathy. Ascites should prompt suspicion of cirrhosis. Jaundice should prompt suspicion of cirrhosis or hepatitis B or C infection. Peripheral edema should prompt suspicion of heart failure.
The appearance of cutaneous lesions, "thrash toes, blue toes", pancreatitis, stroke, ischemic bowel, or angina should prompt suspicion of multiple cholesterol emboli syndrome.
Investigations
Initial investigations include bloods and urinalysis, with specific further investigations guided by clinical features.
Blood tests
Blood urea nitrogen/serum creatinine ratio can help distinguish prerenal from renal causes. A ratio >20 suggests prerenal causes, whereas a ratio <10 suggests renal causes.
Urinalysis
Provides useful diagnostic clues:
Isolated proteinuria suggests nephrotic syndrome, diabetic nephropathy, or preeclampsia. Reagent strips should not be used to identify proteinuria in children and young people.[10] Incidental unexplained proteinuria in adults or children should prompt further investigation for CKD with a creatinine-based estimate of GFR and albumin:creatinine ratio (ACR).[10] ACR is preferred over protein:creatinine ratio (PCR) in patients with CKD because ACR has greater sensitivity for low levels of proteinuria.[10] An ACR of ≥3 mg/mmol is regarded as clinically important proteinuria, but should be confirmed in an early morning sample if it is <70 mg/mmol. An ACR of ≥70 mg/mmol does not need to be checked.[10]
Isolated proteinuria suggests nephrotic syndrome, diabetic nephropathy, or preeclampsia. Spot urine ACR quantifies proteinuria reasonably accurately, and much more easily than a 24-hour urine collection, and should always be ordered as a follow-up to urinalysis showing proteinuria.
Isolated hematuria suggests nephrolithiasis.
Proteinuria and hematuria without other abnormalities suggests acute interstitial nephritis.
Further urine tests include microscopy, specific gravity, osmolality, random urine sodium, and fractional excretion of sodium.
Normal or hyaline casts, specific gravity >1.020, osmolality >500 mOsm/kg H₂O, random urine sodium (UNa) <20 mEq/L, and a fractional excretion of sodium (FENa) <1% suggest prerenal pathology. FENa may be calculated using the following formula: (urine sodium x plasma creatinine)/(plasma sodium x urine creatinine) x 100. [ Fractional Excretion of Sodium Opens in new window ]
Hematuria, proteinuria, red blood cell casts, epithelial cell casts, waxy casts, granular casts, UNa >20 mEq/L, and FENa <1% suggest glomerulonephritis.
Muddy brown granular casts, epithelial cell casts, specific gravity approximately 1.010, UNa >20 mEq/L, and FENa >1% suggest acute tubular necrosis.
Myoglobin casts suggest rhabdomyolysis.
Eosinophiluria suggests atheroembolic disease (cholesterol emboli).
Crystals suggest a crystal-induced nephropathy. Examples include crystalluria in tumor lysis syndrome, calcium oxalate (ethylene glycol intoxication), medications (acyclovir, indinavir, sulfadiazine).
Other investigations are ordered depending on the clinical features and include the following.
Serum creatine kinase: elevated in rhabdomyolysis and multiple cholesterol emboli syndrome. Mild elevation is seen in patients taking creatine supplements.
Blood, urine, and sputum cultures if sepsis is suspected.
Complete blood count: may show anemia in cases of glomerulonephritis associated with systemic disease and patients with heart failure or acute hemorrhage; leukocytosis in infection or inflammatory states.
C-reactive protein or erythrocyte sedimentation rate: may be elevated in systemic inflammation, such as vasculitis.
Serology for underlying infections, including HIV, hepatitis B and C.
Vasculitis markers: antiglomerular basement membrane antibodies (positive in Goodpasture syndrome), antineutrophil cytoplasmic antibodies (positive in small-vessel vasculitis, e.g., granulomatosis with polyangiitis [formerly known as Wegener granulomatosis], polyarteritis nodosa) and antinuclear antibodies or anti-double-stranded DNA antibodies (positive in systemic lupus erythematosus).
Antistreptolysin O or antiDNAse antibodies should be ordered if poststreptococcal glomerulonephritis is suspected.
Antiphospholipase A2 receptor antibodies are highly sensitive and specific for idiopathic membranous glomerulonephritis.[88]
Complement titers are low in postinfectious glomerulonephritis, systemic lupus erythematosus, subacute bacterial endocarditis, cholesterol embolization, essential mixed cryoglobulinemia, and membranoproliferative glomerulonephritis.
Serum and urine protein electrophoresis should be ordered if paraproteinemia is suspected (electrophoresis shows a protein spike corresponding to the monoclonal protein).
Uric acid is elevated in tumor lysis syndrome.
HbA1c is useful to assess glycemic control in people with diabetes.
Coagulation studies: abnormalities can occur in septic shock and after trauma.
Liver function tests may be abnormal and placental growth factor levels low in women with pre-eclampsia.
Plasma aldosterone to renin ratio is <20 in renal artery stenosis.
ECG may show a cardiogenic cause of shock or evidence of left ventricular hypertrophy or underlying coronary artery disease in patients with hypertension or congestive heart failure.
Chest x-ray and echocardiogram are helpful in cases of congestive heart failure.
Imaging studies
The American College of Radiology provides guidelines for the selection of appropriate imaging modalities.[75][89][90]
Renal Doppler ultrasound should be performed if renal artery stenosis or renal vein thrombosis is suspected.
Renal vein thrombosis can also be detected using magnetic resonance venography.
CT abdomen and pelvis with contrast and arteriography should be performed for major blunt trauma with suspected renal infarction.
Renal and urinary tract ultrasound should be performed if obstructive uropathy is suspected. If the suspected cause of obstructive uropathy is renal stones, noncontrast CT is the preferred test.
Renal biopsy
Renal biopsy should be considered as an initial test in patients with uremic symptoms or multiorgan involvement; it provides a definitive diagnosis of underlying renal causes.
In all other patients, renal biopsy is reserved for cases in which confirmation of the diagnosis is required after a systematic investigation is completed.
Estimation and measurement of glomerular filtration rate (GFR)
The most accurate method for calculating GFR is by measuring the clearance of exogenous filtration markers, such as iothalamate, iohexol, or inulin. However, this is expensive and requires exposure to radiation and compliance with strict regulatory guidelines. In practice, therefore, creatinine or cystatin C clearance is used to estimate GFR. See Etiology.
Use of this content is subject to our disclaimer