Abstract
Background: Differential diagnosis between primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is sometimes difficult as nephrotic syndrome is the main clinical symptom in both diseases. Objectives: This study has attempted to evaluate the urinary excretion of Th1 and Th2 cytokines as potential biomarkers in distinguishing the two types of nephrotic syndrome, and predicting outcome of renal function. Patients and Methods: Thirty-six patients with FSGS (M/F 22/14, Age; 41.9 ± 17 years, SCr=1.7 ± 0.8 mg/dL, UProt=4.7 ± 5.5 g/24 h), and 21 with MCD (M/F 5/16, Age; 41.4 ± 15 years, SCr = 1 ± 0.4 mg/dL, UProt = 7.9 ± 9.3 g/24 h) were included in the study. Τh1 (IL-2, IL-12, GM-CSF, INF-γ, TNF-α) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were measured by multiple cytokine assay, Luminex technology, in first morning urinary samples collected at the day of renal biopsy. Results: No significant differences in urinary excretion of all cytokines were found between FSGS and MCD patients. In FSGS however, IL-12 urinary levels were independent factor correlated with both global sclerosis (R = 0.5, P = 0.009) and interstitial fibrosis (R = 0.5, P = 0.02). Th1 cytokines (IL-2 and GM-CSF) were significantly increased in FSGS patients who did not respond to treatment (P = 0.03 and P = 0.007, respectively). Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were significantly increased in MCD patients with frequent relapses (P = 0.05, P = 0.001, P = 0.01, P = 0.03). Conclusions: Urinary excretion of Th1 and Th2 cytokines cannot discriminate FSGS from MCD. Th1 cytokines, especially IL-12, IL-2 and GM-CSF, may be involved in pathology and progression of FSGS, while Th2 cytokines are implicated in frequent relapses of nephrotic syndrome in MCD.
Highlights
Differential diagnosis between primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is sometimes difficult as nephrotic syndrome is the main clinical symptom in both diseases.Article history: Received: 2 October 2016 Accepted: 10 December 2016
Th1 cytokines, especially IL-12, IL-2 and GM-CSF, may be involved in pathology and progression of FSGS, while Th2 cytokines are implicated in frequent relapses of nephrotic syndrome in MCD
In clinical practice very often it is becoming difficult to differentiate between these two primary glomerulopathies, as histology of FSGS includes focal and segmental lesions, that can be missed, and histology of MCD consists of podocyte injury, which is common in both disorders
Summary
Differential diagnosis between primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is sometimes difficult as nephrotic syndrome is the main clinical symptom in both diseases.Article history: Received: 2 October 2016 Accepted: 10 December 2016. The identification of biomarkers in NS would be extremely useful, in many possible ways, including distinction between FSGS and MCD, discrimination of FSGS subtypes (FSGS not-otherwise specified, hilar FSGS, tip-lesion, collapsing, cellular), estimation of response to treatment and renal outcome, prediction of recurrence of FSGS after completing treatment, and after transplantation [8,9]. Metalloproteinase, growth factors, such as epidermal growth factor (EGF) and transforming growth factor (TGF-β1), a1-antitrypsin, fragments of albumin and Tamm-Horsfall protein and miRNAs are few examples of the molecules whose urinary levels can be important in discriminating FSGS and MCD and give information about disease outcome [9,10,11,12,13]. In a healthy environment the preinflammatory reactions of Th1 cytokines as the main contributors in cellular immunity are balanced by the anti-inflammatory activity of Th2 cytokines, the principal actors in humoral immunity [16,17]
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