Two Cases Of Purpuric Nephritis ISKDC Type 6 For Which Prognosis Could Be Predicted Using The Revised Oxford Classification Or Semi-quantitative Classification Ⅱ

Consideration

We experienced two pediatric cases of purpuric nephritis ISKDC type 6 with different clinical and histological features. Case 1 did not exhibit symptoms of abdominal pain after the onset of IgA vasculitis, but hematuria and moderate proteinuria were observed, and a renal biopsy was performed. The kidney tissue showed MPGN-like findings, but all sampled glomeruli showed hypercellular lesions in all nodes. On the other hand, case 2 had severe abdominal pain symptoms immediately after the onset of IgA vasculitis, and the patient was in a nephritic-nephrotic state, and a kidney biopsy was performed. In addition to his MPGN-like findings, his renal histology showed a necrotizing crescentic nephritis-like pattern with very strong extravascular lesions. Even with the same MPGN-like findings, case 1 had a more widespread lesion, and case 2 had a strong local extravascular lesion. Regarding renal prognosis, case 1 chose his IVMP and multidrug therapy, and the clinical course was very favorable. On the other hand, in case 2, he added plasmapheresis treatment to IVMP and multidrug therapy, and the treatment response, including relapse treatment, took time.

Cistanche Supplement Support  Kidney Function Supplement 

Approximately 4 years after the start of treatment, the urinary findings finally returned to normal (clinical remission). He has been in clinical remission for about a year, but the long-term prognosis is unknown because the follow-up period is short and he is still taking ARB, but he will continue to be carefully monitored while paying attention to the recurrence and progression of chronic lesions. It is.

Purpuric nephritis is secondary nephritis complicating IgA vasculitis, and histologically, it shows mesangial proliferative nephritis, similar to his IgA nephropathy, and the fluorescent antibody method shows that his IgA is deposited in the mesangium. 2). Furthermore, the histopathological severity is mainly classified into six categories by ISKDC.

1). This classification is still frequently used today and is classified based on the percentage of glomeruli showing mesangial proliferation and the percentage of crescent formation, which was considered a promising prognostic factor at the time. Among them, type 6 is a special type called MPGN-like characterized by changes in the mesangial region and glomerular capillary walls, and is a relatively rare pathology with a reported incidence of 1.1 to 5.7%1)3). -Five). MPGN-like lesions are also seen in other diseases, but Shigematsu describes this lesion as a condition in which a mesangial region extends out from the shaft along the glomerular snare wall, either circumferentially or partially, and is reversible. It was assumed that irreversible processes were mixed6). The acute lesion of subendothelial mesangial edema is a reversible process in which reconstruction and regeneration of the snare wall can be expected; conversely, the delay in subendothelial mesangial edema, the stagnation of macrophages, and the survival of interstitial mesangial cells are caused by glomerular involvement. The idea is that this can be an irreversible process that progresses to the hardening of the hoof wall.

Table 2 Reported cases of purpuric nephritis type 6 with prognosis (including this case)

On the other hand, there is no established treatment for purpuric nephritis. According to the 2012 KDIGO clinical practice guideline for childhood purpura nephritis, patients with proteinuria >0.5 to 1 g/day/1.73 m2 should receive angiotensin-converting enzyme (ACE) inhibitors or ARBs depending on the treatment response. The recommended treatment guidelines include 6 months of PSL for cases with poor renal function, and additional administration of IVMP or cyclophosphamide (CPA) in cases with crescent formation or decreased renal function7). This guideline is based on his treatment guidelines for chronic IgA nephropathy, but (1) unlike his IgA nephropathy, it is easy to identify the onset time of purpura nephritis, and acute lesions often predominate; ②Main acute lesions

For purpuric nephritis in the body, there is a high possibility that renal prognosis will be improved by active therapeutic intervention centered on PSL. ) inhibitors cannot be expected to have the effect of suppressing inflammation or suppressing crescentic formations, and are recommended for initial administration.

For reasons such as the possibility of misjudging the therapeutic effect from the more apparent effect of reducing proteinuria), we believe that it is not appropriate to use RAS inhibitors from the initial stage unless chronic lesions are the main cause. In fact, at our hospital, we do not use RAS inhibitors from the initial stage but rather use multidrug therapy (PSL, warfarin, mizolibine, and dipyridamole) depending on the severity of acute lesions such as intraductal proliferation, snare necrosis, and crescentic formation. , the treatment policy is to add IVMP and PE. CPA is not used because of the side effects of gonadal disorders.

In order to understand the clinical characteristics, treatment, and prognosis of purpuric nephritis ISKDC type 6, previously reported cases with a prognosis and this case are summarized in Table 2. The prognosis was defined as A: normal, B: urinary abnormalities only, C: active nephritis (hypertension, renal dysfunction, urinary abnormalities), D: end-stage renal disease, and E: death. From this table, 26 cases are small

At least 18 patients reached a nephrotic state at onset, suggesting a tendency to present with large amounts of proteinuria. Furthermore, whereas in the past there were many cases with a poor prognosis such as death or end-stage renal failure, recent reports have shown that there were many cases with a relatively good prognosis. It is possible that the prognosis has improved due to enhanced treatments such as IVMP and plasma exchange, and cases of purpuric nephritis ISKDC type 6 are not necessarily intractable.

The ISKDC classification has been criticized for its problems, including that the degree of crescent formation does not necessarily correlate with renal prognosis,3),12)-14) and tubulointerstitial lesions and surrounding vascular lesions are not evaluated. I came 14)15). Subsequently, it was shown that the proportion of sclerotic glomeruli and interstitial fibrosis correlated better with long-term outcome16).

It has been concluded that the Oxford classification used for IgA nephropathy can predict the progression of purpuric nephritis. The Oxford classification was revised in 2016 and includes traditional mesangial hypercellularity (M), intracapillary proliferation (E), segmental glomerulosclerosis/adhesions (S), and tubular atrophy/interstitial fibrosis (T). The C (crescent score) was added to the MEST, and the S score was revised to take into account the presence or absence of characteristics of podocyte damage17). Table 3 shows cases of purpuric nephritis that have been applied to the (revised) Oxford classification and have been shown to be associated with renal prognosis. Of the 4 articles retrieved, 2 were for adults and 2 were for children, and there were many reports that S and T, which are not involved in ISKDC classification, were significantly correlated with renal prognosis, and the final conclusion was that ( The revised Oxford classification has been shown to be useful for predicting renal prognosis. In addition, there were no cases of ISKDC type 6 in these papers. On the other hand, against this background, the introduction of various semi-quantitative classifications has also been reported. For example, Koskela et al. compared his ISKDC classification with semiquantitative scoring (SQC), which takes into account more than 14 variables, for 53 children with purpuric nephritis. Long-term prognosis can be improved by setting the SQC cutoff value to 10.5.

reported that it is possible to divide patients into a good prognosis group and a poor prognosis group22).

Applying the revised Oxford classification to this case, case 1 is M(1)E(1)S(0)T(0)-C(0), and case 2 is M(1)E(1)S(0). The result is T(0)-C(2), and in both cases E is 1, which is likely to respond to immunosuppressants such as steroids, and among lesions MST that have an influence on prognosis independently of clinical parameters, only M is 1. Case 2 had a C score of 2, which is a lesion that affects prognosis when immunosuppressants are not administered. In general, it was assumed that the prognosis for both cases was not bad if treatment centered on immunosuppressants such as steroids was performed. Similarly, when evaluated by Koskela et al.'s SQC, case 1 received a score of 3 points, and case 2 received a score of 7 points.

All cases were below the cutoff value, and the long-term prognosis was predicted to be good. These two cases are classified as purpuric nephritis ISKDC type 6, but in both cases, chronic lesions such as primary histological segmental sclerotic lesions and interstitial fibrosis were not observed, but intraductal proliferation, snare necrosis, and Intensity of acute phase findings such as crescent formation

Treatment for case 2 was strengthened. However, as mentioned above, the ISKDC classification is mainly classified by the degree of crescent formation, which does not necessarily correlate with renal prognosis, and type 6 in particular is a special type of MPGN-like lesion, so purpura nephritis is classified not only by the ISKDC classification. , we recognized the importance of selecting treatment in combination with other classifications and scoring that can predict prognosis. Lupus nephritis, like purpura nephritis, is another inflammatory kidney disease, but the classification systems in use are related to the severity of kidney disease and renal outcome, making treatment strategies based on histological classification difficult. Established23)24). In addition to the ISKDC classification, an appropriate classification related to the severity of renal disease and renal outcome is also desired for purpuric nephritis.

Conclusion

Purpuric nephritis ISKDC type 6 is a relatively rare condition, but it is diverse and does not necessarily have a poor prognosis. I think it is important to evaluate the severity by reclassifying and semi-quantifying the clinical symptoms and histological findings at the time of onset, and to provide stratified treatment without unifying treatment. I was hit.

Acknowledgment

We would like to express our deepest gratitude to Dr. Asami Takeda, Department of Nephrology, Japanese Red Cross Society Aichi Medical Center Nagoya Second Hospital, for her interpretation of the renal histopathology and comments.

Documentation

1) Counahan R, Winterborn MH, White RH, Heaton JM, Meadow SR, Blett NH, Swetschin H, Cameron JS, Chantler C: Prognosis of

Henoch-Schönlein nephritis in children. Br Med J 1977; 2: 11-14.

2) Kuno Toshi: Purpura nephritis (IgA vasculitis). Revised edition of the pathology of kidney disease Atorosu. Japanese Renal Pathology Society, Japanese Renal Society, ed. Tokyo, Tokyo Medical Society, 2017: 119-125.

3) Soylemezoglu O, Ozkaya O, Ozen S, Bakkaloglu A, Dusunsel R,Peru H, Cetinyurek A, Yildiz N, Donmez O, Buyan N, Mir S, ArisoyN, Gur-Guven A, Alpay H, Ekim M, Aksu N , Soylu A, Gok F, Poyrazoglu H, Sonmez F: Turkish Pediatric Vasculitis Study Group. Henoch-Schönlein nephritis: a nationwide study. Nephron Clin Pract 2009; 112: c199-204.

4) Kawasaki Y, Suyama K, Yugeta E, Katayose M, Suzuki S, Sakuma

H, Nemoto K, Tsukagoshi A, Nagasawa K, Hosoya M: The incidence and severity of Henoch-Schönlein purpura nephritis over a 22-year period in Fukushima Prefecture, Japan. Int Urol Nephrol 2010; 42: 1023-1029.

5) Huang YJ, Yang XQ, Zhai WS, Ren XQ, Guo QY, Zhang X, Yang

M, Yamamoto T, Sun Y, Ding Y: Clinicopathological features and prognosis of membranoproliferative-like Henoch-Schönlein purpura

nephritis in children. World J Pediatr 2015; 11: 338-345.