Our patient underwent a renal biopsy at the time of initial diagnosis of NS, which pathologically revealed MCD. MCD is considered to be a benign disease with a favorable long-term prognosis and a rare tendency to progress to ESRD. There was no glomerular injury under light microscopy, and only the foot process of podocytes disappeared under electron microscopy, but not the loss of the podocytes themselves. Although the proportion of adult-onset MCD patients in NS is low, unlike children, it is less responsive to corticosteroids and more prone to AKI. Moreover, steroid-resistant MCD patients may progress to ESRD, and these patients may be missed FSGS patients. In contrast to MCD, patients with FSGS have a higher risk of corticosteroid-resistant and renal failure. Irreversible glomerular damage caused in the context of FSGS can be explained by podocyte depletion. Compensatory hypertrophy of the remaining podocytes, cell-to-cell propagation of podocyte injury, and segmental solidification of the glomerular tuft can lead to progressive focal and segmental sclerosis[5, 9].
As far as we know, cases of transition between MCD and FSGS are not rare in clinical practice, but few cases have been reported. Only some cases have appeared in observational studies without in-depth analysis, and most of these studies were concentrated in children or adolescence [10, 11, 12]. In the above literature, most scholars may prefer to have FSGS at the beginning of the disease. The focal and segmental nature of FSGS leads to sample error or diagnosis error, resulting in misdiagnosis of MCD or missed diagnosis of FSGS. We agree that, especially in patients with early lesions or few glomeruli in biopsy specimens. Early FSGS could only show the diffuse effacement of the foot process, which was consistent with MCD. There was no difference in the decrease of podocyte density labeled by WT1 between MCD and FSGS. These factors can result in confusion of the two diseases for clinicians. In fact, FSGS lesions may be absent in the early stages of NS, and the presence of FSGS lesions in repeated biopsy tissue reflects the progression of MCD. The dose dependence of animal models supports the hypothesis that MCD and FSGS are two successive pathological processes of podocyte disease. Both models are based on the induction of podocyte injury and subsequent podocyte loss, and the difference depends on the degree of podocyte injury and severity of podocyte loss. Only foot process of podocyte exfoliation similar to MCD is observed at the initial phase, while persistent podocyte loss results in the development of FSGS. In the initial stages, this disease is steroid-sensitive. With relapse and delay, continuous proteinuria and podocyte loss lead to decreased or lost of steroid sensitivity. When the loss of podocytes is more than 30–40%, the outcome of ESRD seems inevitable . In this case, after the diagnosis of MCD, the patient was treated regularly with corticosteroid and achieved complete remission. Although there was no regular follow-up later, at least it was not a serious relapse, according to his description. It has been 20 years since the typical NS recurrence, and his clinical course and repeated renal biopsy results both support FSGS. In order to avoid misdiagnosis, we found the kidney tissue from 20 years ago for re-pathological examination, and the results still support MCD. Therefore, we infer that the patient progressed from MCD to FSGS, rather than a missed diagnosis of FSGS at the first diagnosis.
It is no coincidence that pathological changes occurred before and after repeated renal biopsy. Primary FSGS is usually caused by circulating factors, and the aetiology of secondary FSGS includes infection, drugs, maladaptive responses, familial /genetic form, variation of APOL1 gene and so on[15, 9]. The patient did not have the above background, but a suspiciously related factor was his occupation. He was an electric welder with excessive levels of cadmium and lead in his blood. We have reason to suspect that his aggravation of pathology or the occurrence of ESRD was related to metal nephrotoxicity. The nephrotoxicity induced by excess exposure to certain metals is well known, and lithium has been shown to cause FSGS. Cadmium and lead exposure to the kidney mainly causes proximal renal tubule dysfunction, acute exposure can lead to Fanconi syndrome, and long-term exposure leads to the persistent decline of renal function[17, 18]. Although there is not enough literature to confirm that lead and cadmium can cause FSGS, it has been proved that both of them have podocytotoxicity and even induce podocyte apoptosis [19, 20]. Lead and cadmium can increase the risk of chronic kidney disease respectively, and the combination of the two has more profound nephrotoxicity . The above may explain the positive urine sugar of the patient, and presumably, it may be the reason for the occurrence of ESRD in this patient.
Unfortunately, the patient ultimately required renal replacement therapy, but this case was thought-provoking. MCD and FSGS are both representative podocyte diseases, clinically presenting as sudden-onset NS, characterized by absence of immune deposits in immunofluorescence. However, their treatment responses and the prognosis are quite different. The differential diagnosis of MCD and FSGS is difficult, but it is very important to distinguish between the two. A positive attitude toward a second or multiple renal biopsies is needed for uncertain or recurrent MCD patients and early FSGS patients. In addition to the invasive operation of renal puncture, urinary myo-inositol, PEC marker staining and IgG/albumin staining ratio in tPRD are also potential diagnostic markers to differentiate MCD and FSGS[23, 24, 25].