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Clinical investigation of renal disease 

Clinical investigation of renal disease

Chapter:
Clinical investigation of renal disease
Author(s):

A. Davenport

DOI:
10.1093/med/9780199204854.003.2104_update_006

Update:

Estimation of glomerular filtration rate – equations combining use of serum creatinine and serum cystatin C measurements.

Updated on 30 Jul 2015. The previous version of this content can be found here.
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date: 30 March 2017

An accurate history and careful examination will determine the sequence and spectrum of clinical investigations required to make a diagnosis or decide on prognosis or treatment.

Examination of the urine

Midstream urine (MSU) sample—this standard investigation requires consideration of: (1) macroscopic appearance—this may be suggestive of a diagnosis, e.g. frothy urine suggests heavy proteinuria; (2) stick testing—including for pH (<5.3 in an early-morning specimen makes a renal acidification defect unlikely), glycosuria, specific gravity (should be >1.024 in an early-morning or concentrated sample), nitrite (>90% of common urinary pathogens produce nitrite) and leucocyte esterase; and (3) microscopy—for cellular elements (in particular red cells, with the presence of dysmorphic red cells detected by experienced observers indicative of glomerular bleeding), casts (cellular casts indicate renal inflammation), and crystals.

Quantification of proteinuria—this is important because the risk for progression of underlying kidney disease to endstage renal failure is related to the amount of protein in the urine. Quantification by 24-h urinary collection is cumbersome and unreliable in many patients, and has been replaced by estimation of the urinary albumin:creatinine ratio (ACR; normal is <2.5 mg/mmol for men and less than 3.5 mg/mmol for women) or protein:creatinine ratio (PCR; normal is <13 mg/mmol) on a spot sample. An ACR of 100 mg/mmol approximately corresponds to proteinuria of 1.5 g/day, and 350 mg/mmol to nephrotic-range proteinuria.

Low-molecular-weight proteinuria—is caused by proximal tubular injury and can be detected with markers including α‎-glutathione-S-transferase, α‎1-macroglobulin, and retinol-binding protein.

Estimation of glomerular filtration rate

Knowledge of the glomerular filtration rate (GFR) is of crucial importance in the management of patients, not only for detecting the presence of renal impairment, but also in the monitoring of all patients with or at risk of renal impairment, and in determining appropriate dosing of those drugs cleared by the kidney. Measurement of plasma creatinine remains the standard biochemical test used to assess renal function.

Estimating the glomerular filtration rate (eGFR)—from a measurement of plasma creatinine concentration, the standard method uses the simplified Modification of Diet in Renal Disease (sMDRD) formula, which was based on a predominantly Caucasoid North American cohort with chronic kidney disease, and requires knowledge of the patient’s sex, age, and ethnicity (but not their weight or height). On the basis of the eGFR, stages of chronic kidney disease (CKD) are classified as follows:

Limitations of the eGFR—this has not been validated in people below 18 years of age, hospitalized patients, or those with acute kidney injury, pregnancy, oedematous states, muscle-wasting disorders, amputations, or malnourishment. Similarly, it has not been validated for extremes of age or body weight, or for ethnic groups other than whites of northern European origin and African-Americans. Because of the inaccuracy of the MDRD equation, particularly for those with eGFRs greater than 60 ml/min, a revised version (CKD-EPI) has been introduced.

Other methods of measuring GFR—isotopic methods can provide the most accurate determination of GFR, but are not often required in routine clinical practice. Estimation of creatinine clearance with a 24-h urinary collection remains a useful test, particularly when there is reason to doubt the validity of the eGFR.

Investigation of tubular function

Proximal tubule—analysis of excretion of the following substances can assist in the diagnosis of proximal tubular disorders: (1) glucose—the maximum reabsorption rate for glucose (TmG) in the proximal tubule can be determined following infusion of 20% dextrose and is normally about 15 mmol/litre (TmG/GFR); (2) phosphate—the theoretical maximum tubular threshold of phosphate (TMP/GFR) can be estimated by formula from the plasma and urinary phosphate and creatinine concentrations, or can be measured directly following infusion of phosphate; and (3) amino acids—five types of renal aminoaciduria are distinguished: dibasic amino acids, neutral amino acids (monoaminomonocarboxylic acids), glycine and imino acids, dicarboxylic amino acids, and generalized amino aciduria (Fanconi’s syndrome).

Distal tubule—a water-deprivation test can help to distinguish patients with primary or secondary nephrogenic or cranial diabetes insipidus from those with primary polydipsia, who may all present with polyuria.

Renal-induced electrolyte and acid–base imbalances— (1) estimation of urinary free-water clearance is useful in the analysis of patients with hyponatraemia (see Chapter 21.2.1); (2) estimation of transtubular potassium gradient (TTKG) is advocated by some as useful in analysis of disorders of potassium homeostasis (see Chapter 21.2.2); (3) tests of urinary acidification are discussed in Chapters 21.14 and 21.15.

Renal imaging

Ultrasonography—this noninvasive, safe, versatile and (relatively) inexpensive technique is the first-line method for imaging the kidney and urinary tract in many clinical circumstances.

Ultrafast multislice CT scanning—this allows resolution of 2 to 3 mm or less and has become the mainstay of renal imaging. CT urography can be performed with a combination of unenhanced, nephrogenic-phase, and excretory-phase imaging: the unenhanced images are ideal for detecting urinary calculi; renal masses can be detected and characterized with the combination of unenhanced, nephrogenic- and excretory-phase imaging; the excretory phase provides imaging of the urothelium. CT angiography is the first-line investigation in the evaluation of acute renal trauma, assessment of tumour blood supply in cases of nephron-sparing surgery, and for the diagnosis of renal artery stenosis and/or aneurysms.

MRI—this is an alternative to CT scanning in patients who are allergic to conventional iodine-based radiocontrast media and has particular value in the staging of renal carcinoma and assessment of complex renal cysts. Magnetic resonance angiography (MRA) tends to overemphasize the significance of stenoses. Gadolinium contrast scanning should be carefully considered in patients with eGFR below 30 ml/min because of the risk of nephrogenic systemic fibrosis, which limits the utility of magnetic resonance techniques for many renal patients.

Renal nuclear medicine scanning—(1) dimercaptosuccinic acid (DMSA), used in estimation of differential renal function and detection of scarring (usually associated with reflux); (2) mercaptoacetyltriglycine (MAG3), used in detection of functionally significant obstruction, estimation of differential renal function, screening for renal artery stenosis, and monitoring of renal transplants.

FDG-PET scanning combines the functional aspects of a nuclear medicine scan with the anatomical definition of CT scanning and is used to investigate renal tumours and to diagnose and monitor large vessel vasculitis.

Invasive techniques—these can allow therapeutic intervention as well as diagnosis, including antegrade or retrograde ureteropyelography (insertion of stents to relieve urinary obstruction) and angiography (angioplasty or stenting of the renal artery).

Renal biopsy

A renal biopsy should be considered in any patient with disease affecting the kidney when the clinical information and other laboratory investigations have failed to establish a definitive diagnosis or prognosis, or when there is doubt as to the optimal therapy. However, renal biopsy has the potential to cause morbidity and (on rare occasions) mortality, hence its risk must be outweighed by the potential advantages of the result to the individual patient. Biopsies which would be ‘of interest’ but ‘not in the patient’s interest’ should not be performed.

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