|Year : 2022 | Volume
| Issue : 4 | Page : 317-321
Interpretation of urine routine report of a diabetic patient: A review
Prabhat Agrawal1, Shoorvir Singh1, Mudit Khurana2, Kanika Agarwal3, Nikhil Pursnani3, Ashish Gautam4
1 Department of Biotechnology, G.L.A University, Mathura, India
2 Department of Nephrology, S.N. Medical College, Agra, India
3 Department of Medicine, S.N. Medical College, Agra, India
4 Department of Medicine, Rani Durgawati Medical College, Banda, Uttar Pradesh, India
|Date of Submission||16-Aug-2022|
|Date of Decision||28-Sep-2022|
|Date of Acceptance||06-Oct-2022|
|Date of Web Publication||21-Dec-2022|
Dr. Nikhil Pursnani
Department of Medicine, S.N. Medical College, Agra, Moti Katra, Agra, Uttar Pradesh 282002
Source of Support: None, Conflict of Interest: None
Introduction: Diabetic patients are at an increased risk of multiple complications, among which one of the most dreaded complications is diabetic nephropathy. Early diagnosis and appropriate management will at least prolong the life of the kidney and prevent the development of end-stage renal failure. Materials and Methods: Simple urinalysis is a useful tool for early diagnosis of diabetic kidney disease and helps differentiate between diabetic and nondiabetic kidney diseases. In this review, we have discussed the usefulness of urinalysis for a diabetic patient. Results: Early detection of an abnormality can be an alarming sign, and we can diagnose treatable causes of renal failure in diabetic patients. Conclusions: History, examination, and urinalysis are sufficient in most of the cases for diagnosing diabetic kidney disease. Renal biopsy is indicated in special situations where diagnosis cannot be made even after appropriate non-invasive investigations. Few limitations of the study are resource settings and knowledge of this simple test to predict an alarming sign of the kidney disease.
Keywords: ACR, albuminuria, diabetic kidney disease, hematuria, pyuria, urine analysis
|How to cite this article:|
Agrawal P, Singh S, Khurana M, Agarwal K, Pursnani N, Gautam A. Interpretation of urine routine report of a diabetic patient: A review. J Diabetol 2022;13:317-21
| Introduction|| |
With the increasing prevalence of diabetes mellitus, there is a substantial increase in its microvascular as well as macrovascular complications.
Diabetes is the most common cause of chronic kidney disease or end-stage renal disease (ESRD) due to multiple mechanisms such as glomerular hyperfiltration, oxidative stress due to advanced glycation products, increased vascular proliferation mediated by an increase in vascular endothelial growth factor (VEGF), interstitial fibrosis, and atrophy of tubules with an advancement of the disease leading to a decrease in estimated glomerular filtration rate (eGFR).,, However, it is almost impossible to clearly predict the prevalence of diabetic kidney disease (DKD) as it is a diagnosis of biopsy, which being an invasive procedure is infrequently performed. Therefore, the diagnosis of DKD is presumed to have been based on the clinical history and laboratory evaluation. Although diabetic patients mostly experience diabetic nephropathy, they might also present with other renal disorders, pathologically unrelated to diabetes known as nondiabetic kidney disease (NDKD).
Diabetic nephropathy is characterized pathologically by a thickening of glomerular basement membrane, endothelial damage, mesangial expansion, nodule formation, and podocyte loss. But, the term “Diabetic kidney disease (DKD)” is clinically defined as the presence of persistently high urine albumin-to-creatinine ratio (ACR) more than/equal to 30 mg/g and/or the sustained reduction in eGFR below 60 mL/min per 1.73 m2. DKD is further divided into stages that are elaborated in [Figure 1].
| Screening for Kidney Disease in Diabetics|| |
In general, patients suffering from diabetes have a higher risk of kidney injury, cardiovascular mortality, and all-cause mortality as compared to nondiabetics, necessitating early diagnosis and expeditious management, but the relative risk of health outcomes is similar in both. Proteinuria-lowering drugs might be renoprotective; therefore, assessing proteinuria is an important aspect of monitoring treatment response in all patients. Ergo, urinalysis serves to be one of the most important investigations to diagnose DKD early as well as to assess the disease severity, and it also helps differentiate from nondiabetic causes of kidney disease in diabetic patients that might be mistaken for diabetic nephropathy. Urinalysis is an easy-to-conduct, noninvasive method for early identification of the disease, which helps prevent the further progression of the disease as regardless of etiology. Chronic kidney disease is classified according to the combined measures of albuminuria and eGFR to indicate prognosis for acute kidney injury, progressive kidney disease, renal failure, cardiovascular mortality, and all-cause mortality. In patients at high cardiovascular risk, the incidence of cardiovascular events is approximately 2.5 times higher for every 10-fold increase in urine albumin excretion and approximately two-fold higher for every halving of eGFR. Early institution of therapy will help reverse the albumin loss at the level of glomerulus and improve eGFR, decreasing the incidence of cardiovascular mortality and further complications.
| Urine Analysis in Diabetics|| |
Urine analysis should be done annually in all the patients with type 2 diabetes mellitus from the point of diagnosis and in type 1 diabetics beginning 5 years after the diagnosis unless the patient has hypertension, which if present, then urinalysis should be done earlier. Routine screening in diabetic patients includes albuminuria detection in urine (spot urine albumin creatinine ratio (UACR), 24-h urinary protein), complete urine analysis, and estimated glomerular filtration rate (GFR).
| Detection of Albuminuria in Urine|| |
Urinary albumin measurements are more sensitive and specific for changes in glomerular permeability as compared to total urinary protein as well as the standardization of albumin is easier as compared to total protein., It can be done by using quantitative measure: albumin excretion rate (AER), ACR, protein excretion rate (PER), protein/creatinine ratio (PCR), and by staging it into mild, moderate, and severe as depicted in [Table 1]. Urinary ACR values were chosen as they have a better correlation with 24-h urinary albumin measurement and urinary ACR preferred over PCR because of better standardization.
Mildly increased albuminuria (<30 mg/g or mg/day)
Moderately increased albuminuria (30–300 mg/g or mg/day)
Moderately increased albuminuria, which was earlier named as microalbuminuria, is defined as either an estimated or measured urine albumin excretion between 30 and 300 mg/g or mg/day. The change in terminology was to signify that the importance of the presence of any amount of albumin is dangerous as the increase in the amount (even below the threshold for moderately increased albuminuria) forecasts a higher risk for future kidney and cardiovascular disease.
Relationship between PER and PCR and that between AER and ACR are dependent on the assumption that an average creatinine excretion rate is 10 mmol/day or 1 g/day.
Severely increased albuminuria (>300 mg/g or mg/day)
Previously termed macroalbuminuria, it is described as either an estimated or a measured urine albumin excretion >300 mg/g or mg/day.
It provides forecast for the increased severity of disease with worsening in GFR, or the development of ESRD. Severely increased albuminuria may also provide clue for the presence of other kidney pathology instead of DKD and therefore warrants further evaluation.
| Components of Routine Urinalysis|| |
The first early morning urine sample is more concentrated and therefore has better chances of the detection of sediments, but due to chronic stasis, there is also an increased risk of lysis of cells.
Because of the same reason, mid-stream of the second urine sample in morning is preferred in all the patients. Mid-stream sample also decreases the contamination with vaginal secretions in females. Urine sample should be examined within 2 h of collection; otherwise, cell lysis ensues. If required, the sample can be preserved at 2°C–4°C up to 24 h.
Complete urinalysis consists of the following three components:
- 1. Gross assessment of the urine
- • Urine color
- • Turbidity
- • Urine odor
- 2. Urine dipstick analysis
- • Specific gravity
- • pH
- • Protein
- • Glucose
- • Ketone
- • Blood (heme)
- • Urobilinogen
- • Nitrite
- • Leukocyte esterase
- 3. Urine sediments (microscopy)
- i. Cells
- • Red blood cells (RBC)
- • White blood cells (WBC)
- • Epithelial cells
- ii. Casts
- • RBC cast
- • WBC cast
- • Granular cast/waxy cast
- • Renal tubular epithelial cells
- iii. Crystals and microorganisms
| Differentiating Features between Diabetic Kidney Disease and Nondiabetic Kidney Disease Using Urinalysis|| |
The prevalence of NDKD ranges in diabetics ranges from 10% to 85% in different literature. As per the study performed at the Columbia University, approximately 24% of all the native kidney biopsies were taken from diabetic patients, 37% of which had DKD alone, 36% had NDKD alone, and 27% had both DKD with NDKD. In the DKD with NDKD group, the most common finding was acute tubular injury, whereas in the group with NDKD alone, the most frequent diagnosis came out to be focal segmental glomerulosclerosis.
- 1. Microscopic hematuria and active urinary sediments: Urine sediment in diabetic nephropathy is usually bland, but microscopic hematuria can occur. In a report from Japan, glomerular hematuria was observed in 17% patients of diabetes mellitus and almost half of these had NDKD, but hematuria was also observed in a minority of DKD patients. More severe diabetic nephropathy changes were observed on renal biopsy if hematuria was present. Although sensitivity and specificity of microscopic hematuria for detecting NDKD are poor, the presence of dysmorphic RBC in the urine is highly specific (94%) for NDKD. The evaluation of spun urine on high-power microscope reveals dysmorphic RBCs varying in size, shape, and hemoglobin content, thereby revealing glomerular hematuria, whereas isomorphic RBCs reflect nonglomerular bleed (from lesions such as calculi, papilloma, carcinoma, etc.). Glomerular versus nonglomerular hematuria can further be differentiated on the basis of clinical features, examination, and lab criteria as discussed in [Table 2].
- 2. Onset of proteinuria: The onset of proteinuria within 5 years from the documented onset of diabetes mellitus is suspicious of NDKD, because the latent period of overt diabetic nephropathy is usually 10–15 years. Though, the time of onset is difficult to ascertain in patients of type 2 diabetics.
- 3. Heavy proteinuria: An average healthy adult does not excrete more than 150 mg of total protein per day, consisting of 20–30 mg of albumin, 10–20 mg of low molecular weight protein that has undergone glomerular filtration, and 40–60 mg of proteins secreted by the distal tubules such as Tamm-Horsfall protein. Proteinuria can be detected by reagent strip test, which is based on the effect of albumin on a buffer, causing a change in pH proportional to the concentration of albumin itself. Color changes can help in the semi-quantitative analysis of albuminuria. Heavy proteinuria may be an indication of NDKD and therefore warrant further investigation including biopsy.
- 4. Rapid progression of disease: Diabetic nephropathy is a slowly progressive disorder, and rapid deterioration suggests NDKD.
- 5. Morphology of RBC: The presence of dysmorphic RBC in the urine is highly specific (94%) for NDKD.
- 6. Sudden increase in proteinuria: A sudden increase in albuminuria of greater than 5- to 10-fold or eGFR decline of greater than 5 mL/min/1.73 m2 per year.
- 7. Discrepancy between total urinary protein and dipstick albumin: Dipstick test detects only albumin in the urine; therefore, the presence of other proteins such as free light chain may be missed and therefore increased total protein in the urine helps in the diagnosis.
- 8. Pyuria: Diabetes is an immunocompromised state exposing the patient to the threat of recurrent infection; therefore, urinary tract infection is common in diabetics. On routine urine examination, it can be easily revealed as the presence of pus cells. Pyuria is defined as the presence of:
- (a) 10 or more WBC per mm3 in an unspun specimen of urine
- (b) Three or more WBC per mm3 of spun specimen of urine
- (c) Urinary dipstick analysis that turns out to be positive for leukocyte esterase.
Usually, the culture of such urinary specimens reveals causative organism, but sometimes, there might be sterile pyuria that can be defined as the persistent presence of WBC in the urine with the absence of bacteria, as determined by the means of aerobic laboratory techniques. Sterile pyuria can be due to infective or noninfective causes. Most common cause of sterile pyuria is prior antibiotic use, and therefore cultures should always be sent before the initiation of antibiotics. Other infective causes can be prostatitis, balanitis, urethritis, genitourinary tuberculosis, and fungal infection. WBC can also be present due to inflammation without any infection such as in interstitial nephritis, nephrolithiasis, urothelial tumors, and polycystic kidneys.
- 9. Other features: Proteinuria in the absence of retinopathy (especially in type 1 diabetes) and neuropathy as usually retinopathy precedes the presence of nephropathy.
Such atypical findings on urinalysis warrant further investigation such as abdominal ultrasound, kidney function test, and if indicated, renal biopsy, which are discussed further.
| Clinical Indication for Kidney Biopsy in Diabetics|| |
Kidney biopsy remains to be the gold standard investigation for diagnosis, treatment decisions, and prediction of outcome in patients with kidney disease. But as currently there are no standard guidelines for the indications of biopsy, it is mainly based on the personal opinion of the physician. It is mostly done for patients where it is difficult to differentiate between DKD and NDKD, that is patients presenting with atypical features such as:
- (a) Nephrotic-range proteinuria or kidney failure with duration of diabetes less than 5 years
- (b) Presence of nephrotic-range proteinuria in patients with normal kidney function
- (c) Nephrotic-range proteinuria or kidney failure in the absence of diabetic retinopathy
- (d) Worsening renal functions and the presence of unexplained microscopic hematuria
- (e) Hematuria with a family history of renal disease
- (f) A sudden increase in albuminuria or a rapid decline in eGFR.
Few limitations of the study are resource settings and knowledge of this simple test to predict an alarming sign of the kidney disease.
| Conclusions|| |
Early evaluation of urine in diabetics is a simple, noninvasive, and cost-effective method for diagnosis of kidney disease and to initiate proper management as soon as possible. Recently, multiple methods to quantify proteins have been developed leading to early detection. Albuminuria can be reduced using proteinuria lowering drugs, and eGFR can be improved significantly if therapy is started early in the course of the disease. Urinalysis also helps differentiate patients having kidney disease due to nondiabetic causes, which might be mistaken for DKD. The presence of atypical features in urine warrants further investigation, such as biopsy to identify the cause. Therefore, urinalysis in diabetics is a first and basic investigation that should be done to identify the cause of kidney disease in diabetics.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Brownlee M The pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005;54:1615-25.
Chen TK, Knicely DH, Grams ME Chronic kidney disease diagnosis and management: A review. JAMA 2019;322:1294-304.
Helal I, Fick-Brosnahan GM, Reed-Gitomer B, Schrier RW Glomerular hyperfiltration: Definitions, mechanisms and clinical implications. Nat Rev Nephrol 2012;8:293-300.
Hostetter TH Diabetic nephropathy. Metabolic versus hemodynamic considerations. Diabetes Care 1992;15:1205-15.
National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis2012;60:850-86. Erratum in: Am J Kidney Dis2013;61:1049.
Lamb EJ, MacKenzie F, Stevens PE How should proteinuria be detected and measured? Ann Clin Biochem 2009;46:205-17.
Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, et al
; ADVANCE Collaborative Group. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 2009;20:1813-21.
Zimmet PZ, Magliano DJ, Herman WH, Shaw JE Diabetes: A 21st century challenge. Lancet Diabetes Endocrinol 2014;2:56-64.
Johnson DW, Jones GR, Mathew TH, Ludlow MJ, Chadban SJ, Usherwood T, et al
; Australasian Proteinuria Consensus Working Group. Chronic kidney disease and measurement of albuminuria or proteinuria: A position statement. Med J Aust 2012;197: 224-5.
Bargnoux AS, Barrot A, Fesler P, Kuster N, Badiou S, Dupuy AM, et al
. Evaluation of five immunoturbidimetric assays for urinary albumin quantification and their impact on albuminuria categorization. Clin Biochem 2014;47:250-3.
Zelmanovitz T, Gross JL, Oliveira JR, Paggi A, Tatsch M, Azevedo MJ The receiver operating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy. Diabetes Care 1997;20:516-9.
Summary of recommendation statements. Kidney Int Suppl2013;3:5-14. Doi: 10.1038/kisup.2012.77.
Fogazzi GB, Verdesca S, Garigali G Urinalysis: Core curriculum 2008. Am J Kidney Dis 2008;51:1052-67.
Zhuo L, Ren W, Li W, Zou G, Lu J Evaluation of renal biopsies in type 2 diabetic patients with kidney disease: A clinicopathological study of 216 cases. Int Urol Nephrol 2013;45:173-9.
Sharma SG, Bomback AS, Radhakrishnan J, Herlitz LC, Stokes MB, Markowitz GS, et al
. The modern spectrum of renal biopsy findings in patients with diabetes. Clin J Am Soc Nephrol 2013;8:1718-24.
Julian BA, Suzuki H, Suzuki Y, Tomino Y, Spasovski G, Novak J Sources of urinary proteins and their analysis by urinary proteomics for the detection of biomarkers of disease. Proteomics Clin Appl 2009;3:1029-43.
Hogan JJ, Mocanu M, Berns JS The native kidney biopsy: Update and evidence for best practice. Clin J Am Soc Nephrol 2016;11:354-62.
Gonzalez Suarez ML, Thomas DB, Barisoni L, Fornoni A Diabetic nephropathy: Is it time yet for routine kidney biopsy? World J Diabetes 2013;4:245-55.
[Table 1], [Table 2]