Development of a Kidney Prognostic Score in a Japanese Cohort of Patients With Antineutrophil Cytoplasmic Autoantibody Vasculitis.

Introduction: Glomerulonephritis is frequent in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and crucial to disease outcomes. We conducted a detailed assessment of renal pathology in Japanese patients with AAV, and developed a new score that would predict renal outcome. Methods: Two hundred twenty-one patients who were diagnosed with AAV and underwent a kidney biopsy were enrolled. Data on glomerular, tubular, interstitial, and vascular lesions from kidney biopsies were analyzed; the 3 established classification and prognostic scoring systems (Berden Classification, Mayo Clinic/RPS Chronicity Score [MCCS], and ANCA Renal Risk Score [ARRS]) were validated. Further, we developed a new prognostic score by including variables relevant for Japanese patients with ANCA-glomerulonephritis. Results: Median follow-up was 60 months (interquartile range: 6-60). End-stage kidney disease (ESKD) risk prediction by the MCCS and the ARRS was confirmed. Moreover, our analysis identified 4 items with significant ESKD risk prediction capacity, namely percentage of cellular, fibrocellular, and fibrous crescents; and sclerotic glomeruli. Based on our findings, we created a score evaluating the percentage of these lesions to total glomeruli, the Percentage of ANCA Crescentic Score (PACS). The area under the receiver operating characteristic (ROC) curve evaluating PACS was 0.783. The PACS had a comparable performance as the ARRS in predicting ESKD. The optimal PACS cut-off for ESKD risk over 60 months was 43%. In addition, the percentage of cellular crescents and presence of interstitial inflammation were independent predictors of kidney function recovery. Conclusion: We developed a new score predicting renal prognosis using histopathological data of Japanese patients with ANCA-glomerulonephritis. Studies are needed to validate our results in international cohorts.

Focal segmental glomerulosclerosis with a mutation in the mitochondrially encoded NADH dehydrogenase 5 gene: A case report.

NADH dehydrogenase 5 (ND5) is one of 44 subunits composed of Complex I in mitochondrial respiratory chain. Therefore, a mitochondrially encoded ND5 (MT-ND5) gene mutation causes mitochondrial oxidative phosphorylation (OXPHOS) disorder, resulting in the development of mitochondrial diseases. Focal segmental glomerulosclerosis (FSGS) which had podocytes filled with abnormal mitochondria is induced by mitochondrial diseases. An MT-ND5 mutation also causes FSGS. We herein report a Japanese woman who was found to have proteinuria and renal dysfunction in an annual health check-up at 29 years old. Because her proteinuria and renal dysfunction were persistent, she had a kidney biopsy at 33 years of age. The renal histology showed FSGS with podocytes filled with abnormal mitochondria. The podocytes also had foot process effacement and cytoplasmic vacuolization. In addition, the renal pathological findings showed granular swollen epithelial cells (GSECs) in tubular cells, age-inappropriately disarranged and irregularly sized vascular smooth muscle cells (AiDIVs), and red-coloured podocytes (ReCPos) by acidic dye. A genetic analysis using peripheral mononuclear blood cells and urine sediment cells detected the m.13513 G > A variant in the MT-ND5 gene. Therefore, this patient was diagnosed with FSGS due to an MT-ND5 gene mutation. Although this is not the first case report to show that an MT-ND5 gene mutation causes FSGS, this is the first to demonstrate podocyte injuries accompanied with accumulation of abnormal mitochondria in the cytoplasm.

Pheochromocytoma Diagnosed during the Treatment of Diffuse Alveolar Hemorrhage, a Diagnostic Necessity before Using High-dose Glucocorticoids.

A 46-year-old woman with exacerbating hemoptysis and dyspnea was diagnosed with diffuse alveolar hemorrhage (DAH). High doses of glucocorticoids were initiated, but afterward, paroxysmal hypertension (210/140 mmHg) with headache and abdominal pain appeared. A 50-mm left adrenal tumor with an intense uptake by iodine-123 metaiodobenzylguanidine scintigraphy and catecholamine hypersecretion revealed complication with pheochromocytoma. Because high doses of glucocorticoids, sometimes required for DAH, can provoke life-threatening paroxysmal hypertension in pheochromocytoma and paraganglioma (PPGL), our case suggests that PPGL needs to be recognized as the cause of DAH and should be detected with whole-body imaging before starting glucocorticoids.

Complete remission of diabetic nephropathy in a type 1 diabetic patient with near-nephrotic range proteinuria and reduced renal function.

There is scant knowledge on the changes in renal histological findings in type 1 diabetic patients those initially had nephrotic proteinuria and decreased renal function and later had complete remission of diabetic nephropathy by multifactorial treatment (MFT). A 44-year-old Japanese type 1 diabetic woman (duration of diabetes: 17 years) with massive proteinuria (2.9 g/day) and decreased renal function (creatinine clearance rate (Ccr): 86 mL/min) was admitted. Aggressive MFT was started with intensive insulin treatment, a low protein and low salt diet, angiotensin converting enzyme inhibitor and a diuretic. Her levels of HbA1c decreased to less than 7% within 4 months, and her high blood pressure gradually decreased and remained around mean 116/68 mmHg. Her Ccr level gradually improved and reached 108 mL/min after 78 months. Her first renal biopsy performed before MFT demonstrated diffuse and/or global accumulation of periodic acid-Schiff staining-positive mesangial matrix with increased mesangial matrix/glomerulus ratio and tubulo-interstitial fibrosis. Her second renal biopsy performed 5 years after MFT demonstrated decreased mesangial matrix/glomerulus ratio (42.0+/-4.0% to 29.2+/-1.9% [mean+/-S.D.], p<0.001) and increased her number of glomerular capillaries lumen per glomerulus (47+/-11 to 77+/-12, p<0.006). The number of vascular endothelial growth factor (VEGF)-expressing cells in the glomerular capillary significantly increased. Increased tubulo-interstitial fibrosis and the thickness of glomerular basement membrane (GBM) seen in the first biopsy specimen had decreased in the specimen taken at the second biopsy. Our case provides evidence that glomerular morphological improvements including decreased mesangial deposit and VEGF-related vasculogenesis in response to MFT goes along with functional normalization of diabetic nephropathy, which could not be attained in type 1 diabetic patients that underwent pancreas transplantation.

Two cases of systemic lupus erythematosus complicated by hydronephrosis and unique small structures observed in the glomerular basement membrane.

We report two cases having a similar clinical profile of systemic lupus erythematosus (SLE) complicated by hydronephrosis that developed concurrently with a similar pathological recognition of numerous unique microspherical and microtubular structures in the glomerular basement membrane (GBM). Case 1 refers to a 29-year-old woman with SLE. An increase in the level of proteinuria had been triggered by hydronephrosis. The pathological findings of the kidney revealed "bubbling" of the GBM, microspherical and microtubular structures in the GBM, and a suspicion of podocytic infolding into the GBM. Case 2 refers to a 46-year-old woman with SLE complicated with hydronephrosis. The level of proteinuria had increased, which was followed by renal biopsy. Similar pathological findings detected in Case 1 were also recognized in Case 2. The renal disorder of the two cases exhibited pathological abnormality atypical of lupus nephritis. Histopathological abnormality similar to that detected in the two cases has rarely been reported until recently. The pathogenesis of the GBM lesions of the two cases has not yet been elucidated, but we believe that there is a possibility the persistent mild autoimmune disorder and the concurrence of an obstructive state of the urinary tract may facilitate the occurrence of the pathological abnormality, because the clinical feature of the two cases are conspicuously similar to each other.