Primary membranoproliferative glomerulonephritis (MPGN) was subclassified into three different types based on the morphological patterns. Recently, a diagnostic concept on primary MPGN has changed from those based on only morphology to those that are based on pathogenesis. C3 glomerulopathies (C3GP), which are caused by abnormalities of the complement activation system and are characterized by deposition of only complement C3 in the glomeruli. This review article expounds the concept, definition, clinical features and morphological characteristics of C3GP. At the reclassification on primary MPGN by a concept of C3GP, we are confronting the questions, whether primary MPGN type I with immune complex formation exist and about the procedure of the diagnosis on MPGN type III second form (Anders and Strife type). We discuss these current unsolved problems quoting literature and state future prospects presenting our own cases.

Intrauterine environment influences the health and the risk of non-communicable diseases including chronic kidney disease (CKD) known as the Developmental Origins of Health and Disease (DOHaD) theory. Low birth weight due to intrauterine growth restriction or preterm delivery is a surrogate marker of adverse intrauterine environment, whereas high birth weight is also a risk factor. Reduced nephron endowment is thought to be an important mechanism through which CKD develops, but tubules, interstitium, capillary density, endothelial function, renin-angiotensin system, sympathetic system, response to oxidant injury, inflammation, mitochondrial dysfunction, and epigenetic mechanism may also be involved. Low birth weight worsens the course of various kidney diseases and increases the risk of the development of some diseases. The example of the latter is secondary focal glomerulosclerosis. The development of CKD is associated with catch-up growth, obesity, high salt intake, and resultant hypertension and glucose metabolism disorders. Preventive measures against CKD should start during the intrauterine period. Multidisciplinary approach and education of the population especially child-bearing age women are important.

We retrospectively analyzed the long-term outcomes in 28 children (median (IQR) age, 10.5 (7.7–12.3) years at initial biopsy) with active IgA nephropathy, followed-up at five centers at least 5 years. Active lesions in IgA nephropathy were pathologically defined as endocapillary proliferations, glomerular tuft necrosis, and cellular/fibrocellular crescents. The median urinary protein/creatinine ratio at the time of renal biopsy was 0.79 g/gCr (0.3–1.7). All patients had received intravenous methylprednisolone pulse therapy followed by combination therapy (glucocorticoids, dipyridamole, warfarin, and mizoribine). Additionally, after the initial treatment, three patients received intravenous methylprednisolone pulse therapy, eight received angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers, and five underwent tonsillectomy. At the end of follow-up time, the disappearance rates of proteinuria and hematuria were 85.7% and 67.9%, respectively. No patients developed hypertension and renal insufficiency, and no serious side effects were observed during the follow-up period. Hence, initial intravenous methylprednisolone pulse therapy and additional therapy may be effective and useful in patients with active IgA nephropathy.

We compared the pharmacokinetics of cyclosporine (CsA) when administered as a liquid or capsule to 13 patients with idiopathic nephrotic syndrome who were changed from liquid to capsule. The median age at change of administration was 3.9 years old. There was no significant difference in dose of CsA between liquid and capsule. Compared with capsule, liquid showed a lower maximum blood concentration and slower decrease in blood concentration. All Cmax/dose, C2/dose, AUC0-4/dose were significantly lower with liquid, but AUC0-12/dose did not differ significantly (P=0.15). The correlation between C2 and AUC0-12 was weaker with liquid than capsule (P<0.001). The reason was likely delay in the mixing of bile due to physical factors in liquids. Therefore, when C2 is lower than expected in children administered liquid CsA, it is recommended to evaluation of AUC.

Alport syndrome is a heritable disease that causes progressive renal failure, sensorineural hearing loss, and ocular abnormalities due to a defect in type IV collagen α chains. Microhematuria is the only symptom at the early stage, and therefore, early diagnosis of Alport syndrome is considered difficult. In the case, we detected microhematuria and proteinuria in the urinalysis performed at the age of three years; the first renal biopsy performed at the age of seven years led to the diagnosis of non-IgA mesangial proliferative glomerulonephritis. At the age of eleven years, the patient was suspected to have Alport syndrome based on the thickening/thinning/reticulation of glomerular basement membrane and foam cells revealed by the results of the second renal biopsy. Immunohistochemical staining for type IV collagen confirmed the diagnosis. A genetic analysis revealed an in-frame mutation due to the deletion of 9 nucleobases in COL4A5 exon 21, thus leading to the diagnosis of X-linked inheritance pattern. Our results show that persistent hematuria should be actively considered in the differential diagnosis of suspected cases of Alport syndrome, as the syndrome can only be diagnosed by type IV collagen immunohistochemical staining and genetic analysis.

Mutations in transient receptor potential cation channel 6 (TRPC6) are responsible for the familial forms of focal segmental glomerulosclerosis. We encountered a 2-year-old girl who had proteinuria for 6 months after acquiring group A streptococcal infection. Examination did not indicate she had hypertension, edema, hematuria, renal dysfunction, or hypocomplementemia. We performed a percutaneous renal biopsy when she was 2 years and 6 months old, and focal segmental glomerulosclerosis was suspected. Genetic analysis revealed a TRPC6 mutation. Corticosteroid therapy was not selected as the illness was suspected of being steroid-resistant nephrotic syndrome (SRNS). Although unconfirmed, it is highly likely that SRNS was the cause of her symptoms and that progression to end-stage renal disease is likely in the future. Treatment management was therefore planned with a long-term perspective in mind. She is currently taking ACE inhibitors and her proteinuria persists at 3 years and 6 months after the initial examination.

Adult patients with ANCA-associated vasculitis (AAV) could be often complicated by other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus but which is rare in children. We report two children with microscopic polyangiitis (MPA) complicated by Polyarticular RF-positive juvenile idiopathic arthritis. Case 1 was a 23-year-old female. She developed MPA at the age of 10. She had achieved remission by methylprednisolone pulse therapy (MPT) and intravenous cyclophosphamide. However, arthritis occurred 16 months later and she was diagnosed with pJIA. Methotrexate (MTX) was added and arthritis was resolved.

Case 2 was a 14-year-old female. She developed arthritis at the age of 11. She was diagnosed as having pJIA two years later. She was initially treated with prednisolone, MTX and etanercept. However, she presented hematuria and proteinuria at the age of 14 and was diagnosed with MPA. MPT combined with rituximab significantly ameliorated her symptom. Although concomitance of pJIA and AAV is quite rare, considering its possibility is important when patients developed unexpected clinical symptoms. Furthermore, it is important to choose of therapy which can simultaneously cover both-diseases, especially therapy for MPA is associate with the prognosis.