Diagnostic Tools for Sensitive Estimation of Renal Function & Early Detection of Lupus Nephritis
Journal Title: The Journal of Middle East and North Africa Sciences - Year 2016, Vol 2, Issue 2
Abstract
Introduction: Systemic Lupus Erythematous (SLE) is a systemic autoimmune disease where the immune system mistakenly attacks the body cells and tissues, resulting in a state of chronic inflammation and tissue damage. SLE is characterized by unpredictable course, with periods of flares alternating with remissions. It can affect any part or body tissues, including heart, joints, skin, lungs, liver, nervous system, blood vessels, but still the kidney affection is one of the most commonly involved visceral organs in SLE. Although only approximately 50% of patients with SLE develop clinically evident renal disease, biopsy studies demonstrate some degree of renal involvement in most patients. Acute or chronic renal impairment may develop with lupus nephritis leading to acute or end stage renal disease. Early recognition and management of these cases can reduce the percentage of development of end stage renal disease among these patients to less than 5% of cases. Nephron is the functioning unit of the kidney, whose function is always effected as an early response to inflammation; this function can be evaluated through the estimation of the glomerular filtration rate (secretory function) as well as its excretory function. So searching for a more sensitive and specific indicator for early detection of disease flare or activity depends on the estimation of the nephron function. Aims of the study: The aims of the study are: to evaluate the most sensitive and accurate diagnostic tool to assess glomerular function and glomerular filtration rate (GFR) in lupus nephritis patients, in relation to clinical manifestations and laboratory indices, as a trial for early detection of lupus nephritis, to investigate whether dynamic renal 99mTechnetium Diethylene Triamine Penta Acetic Acid (99mTc-DTPA) Glomerular Filtration Rate (GFR) is a more sensitive indicator of the degree of renal involvement in lupus nephritis patients than laboratory measurement of serum creatinine level and creatinine clearance (CrCl) through estimated Glomerular Filtration Rate (eGFR) formulae, and to assess renal morphology by static renal 99mTechnetium Di-Mercapto Succinic Acid (99mTc-DMSA), as well as split function of both kidneys in view of renal ultrasonography (U/S). Patients & Methods: Twenty-eight patients with biopsy-proven lupus nephritis selected according to WHO classification for renal staging. The disease activity was recorded using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) to detect active disease requiring increased treatment for activity. Immunological profiles, including ANA, anti-dsDNA, complement levels (C3, C4) were assessed. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), creatinine clearance (CrCl), glomerular filtration rate (GFR) using Cockcroft–Gault (CG),the 4-variable abbreviated Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration Formula (CKD-EPI) method, urinalysis with microscopy, 24 hours urinary proteins, as well as total serum proteins and serum albumin were measured. Dynamic 99mTechnetium labeled with Diehtylene Triamine Penta Acetic Acid (99mTc-DTPA) radioisotope renal scan was done for all patients as a part of assessment of renal GFR in all patients in the study group. Another static study was done using 99mTechnetium Di-Mercapto Succinic Acid (99mTc DMSA) to assess the morphological status as well as the split function of both kidneys in view of renal ultrasonography. Results: This study was carried out on 28 patients: 9 males (32.1%) and 19 females (67.9%).Their age ranged from (16 - 44 years) with a mean age (23.57± 9.57 years). Their height ranged from (147 - 169cm) with a mean height (155.14±7.97) and weight ranged from (37- 84.5 kg) with a mean weight (59.66±16.69). As regards the renal histopathology results, 4 patients (14.28%) had mesangial glomerulonephritis, 15 patients (53.57%) had focal proliferative glomerulonephritis, 6 patients (21.42%) had diffuse proliferative glomerulonephritis, and 3 patients (10.71%) had membranous glomerulonephritis. In patients with impaired renal function the 99mTc-DTPA GFR values and C-G estimated GFR values was decreased significantly with P value <0.05, however, that GFR values obtained by the C-G estimated formula showed a total bias (– 15 ml/min/1.73m2) and relative bias (-21%). Whereas, the estimated GFR obtained by MDRD, and CKD-EPI equations are still markedly underestimating the GFR values, among the same group of patients with total bias (-28 & -26 ml/min/1.73m2) and relative bias (-40% & - 37%) respectively. MDRD as well as CKD-EPI equations for estimation of GFR tend to underestimate the GFR value among patients with impaired renal functions. In the patients group with preserved (normal or near normal renal function) the measured GFR by 99mTc-DTPA dynamic renal scintigraphy showed a comparable results to that obtained from the C-G equations total bias (-5 ml/min/1.73m2) and relative bias (-5%), whereas, the GFR values are much higher in equations of MDRD, and CKD-EPI with a total bias (+5 & + 10 ml/min/1.73m2) and a relative bias (+5% & +10%) respectively. MDRD as well as CKD-EPI equations for estimation of GFR tend to overestimate the GFR value among patients with normal or near normal renal functions. There was a significant decrease in the 99mTc-DTPA measured GFR value among patients with stage III and stage IV glomerulonephritis, with a P value < 0.05, Whereas, the GFR values obtained by the C-G formula showed significant decrease only among patients with stage IV glomerulonephritis (P value = 0.016). On the other hand, (MDRD & CKD-EPI formulae) showed insignificant decreased GFR values among patients with stage III & stage IV glomerulonephritis, but they showed significantly increased GFR values among patients with stage II & stage V glomerulonephritis. Conclusion: 99mTc-DTPA as a glomerular agent provides a sensitive, physiological, reliable, accurate and reproducible method for assessment of renal function throughout different disease stages in patients with confirmed diagnosis of lupus nephritis (LN), when compared to other methods evaluating renal function in these patients. It provided a proper evaluation of the nephron function, including renal blood flow condition, the secretory function of the nephrons, as well as nephron's excretory function before and after intravenous diuretics injection. Besides, 99mTc-DMSA as a tubular agent provides a sensitive morphological image of the kidney that can help in estimation of the split function of both kidneys as well as evaluation of the disease course, compared to the traditional morphological imaging modalities (renal ultrasonography).
Authors and Affiliations
Raji Amin, Sami A. Hakim, Hala L. Fayed, Alaa Khalifa, Fouad Khalil, Mahmoud Khedr, Mohamed Alshafee
Keywords
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