An Elderly Case of Minimal Change Nephrotic Syndrome: Correlation between Renal Tubular Dysfunction and the Onset of Oliguric Acute Kidney Injury Requiring Hemodialysis.

Several theories have been proposed to explain the development of severe acute kidney injury (AKI) in patients with minimal change nephrotic syndrome (MCNS), but the exact mechanism remains unclear. We encountered an elderly patient with biopsy-proven MCNS who suffered from oliguric AKI, which required hemodialysis at the onset and during the first relapse of nephrotic syndrome. Throughout her relapse, we were able to monitor tubular injury markers, namely, urinary N-acetyl-ß-D-glucosaminidase and urinary alpha-1-microglobulin levels. This patient had hypertension. 8.5 years after achieving complete remission, she experienced a relapse of nephrotic syndrome accompanied by AKI, necessitating hemodialysis. The hemodialysis was discontinued after 7 weeks of corticosteroid therapy and cyclosporin A treatment. During this relapse, we observed a correlation between the sudden increase in renal tubular injury markers and proteinuria levels and the progression of severe AKI. Conversely, a reduction in renal tubular injury markers and proteinuria was associated with the resolution of AKI. The abrupt elevation of both tubular injury markers and proteinuria levels suggests a possible breakdown in protein endocytosis in proximal tubular cells. Moreover, it is less likely that the acute reduction in intra-glomerular pressure is the primary cause of tubular injury, as it might result in a decrease in both glomerular filtration rate and proteinuria levels. It is conceivable that massive proteinuria, in conjunction with the patient's clinical characteristics, may contribute to tubular injury, ultimately leading to severe AKI in this patient.

Effective Management of Hypertensive Emergencies with Aliskiren Treatment in a Patient Before and After Introducing Hemodialysis Secondary to Scleroderma Renal Crisis-like Condition Under Corticosteroid Treatment for Sjögren Syndrome-associated Multiple Mononeuropathy.

A middle-aged woman presented with hypertensive emergency after corticosteroid treatment for Sjögren syndrome-associated multiple mononeuropathy with suspected systemic sclerosis. Hypertensive heart failure with hyperreninemia improved with antihypertensives, including aliskiren; however, she became hemodialysis-dependent. Clinical findings and biopsy-proven thrombotic microangiopathy indicated conditions resembling scleroderma renal crisis (SRC). Severe hypertension and heart failure with hyperreninemia occurred after stopping aliskiren for hypotension due to diverticular bleeding, which improved after the reintroduction of aliskiren. Aliskiren appears to be effective in managing hypertensive heart failure in patients with SRC. Nevertheless, hemodialysis remained necessary in our case, and whether or not aliskiren can restore the renal function is unclear.

Discontinuing Hemodialysis through Corticosteroid Treatment in a Patient with Cryofibrinogen-associated Glomerulonephritis.

Cryofibrinogen-associated glomerulonephritis (CryoFiGN) is rare, and its diagnosis is difficult while treatment is not established. We herein report an elderly woman with CryoFiGN who experienced recurrent purpura and nephritic features that subsequently progressed to nephrotic syndrome and required hemodialysis during the 18-month clinical course. The patient was treated with corticosteroids, which led to the discontinuation of hemodialysis. The diagnosis of CryoFiGN was based on the clinical presentation, characteristic glomerular deposits, and results of laser microdissection and liquid chromatography-tandem mass spectrometry of the glomeruli. This case highlights the potential utility of corticosteroids as a treatment option for patients with CryoFiGN, even after hemodialysis.

Slowly Progressive ANCA-associated Glomerulonephritis with Strong Mesangial MPO Deposits Following a Diagnosis of Interstitial Lung Disease: A Case Report.

An elderly woman showed positive conversion of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCAs) following the diagnosis of interstitial lung disease (ILD) and glomerular hematuria and subsequently experienced slowly progressive glomerulonephritis. A kidney biopsy revealed chronic damage and necrotizing crescentic glomerulonephritis with mesangial MPO deposits. After corticosteroid treatment, the patient's urinalysis results and MPO-ANCA titers almost normalized and her renal function stabilized. This case is similar to recently reported cases of slowly progressive ANCA-associated glomerulonephritis. ILD likely triggered the production of MPO-ANCAs, and the accumulation of MPO deposits in the glomeruli may have contributed to the progression of her renal disease.

A Diagnostic and Therapeutic Dilemma Concerning Exostosin 1/Exostosin 2-associated Lupus-like Membranous Nephropathy with Positive Antinuclear Antibody in an Elderly Man with Various Immune Abnormalities.

Exostosin 1 (EXT1) and exostosin 2 (EXT2)-associated membranous nephropathy (MN) may be associated with active autoimmune disease. We encountered an elderly man who presented with EXT1/EXT2-associated lupus-like MN with full house immune deposits, monoclonal gammopathy of uncertain significance and Sjögren's syndrome. The patient exhibited various other immune abnormalities. Although he did not fulfill the criteria of clinical systemic lupus erythematosus (SLE), he met a stand-alone renal criterion of the Systemic Lupus International Collaborating Clinics (SLICC) 2012. Whether or not a stand-alone renal criterion with EXT1/EXT2 positivity, as in the present patient, can efficiently guide decisions regarding the diagnosis and treatment of SLE remains a clinical dilemma.

Tubulointerstitial B-cell infiltration and tertiary lymphoid tissue in adult-onset immunoglobulin A vasculitis with nephritis.

PURPOSE: This study aimed to examine tubulointerstitial B-cell infiltration in patients with adult-onset immunoglobulin A vasculitis (IgAV) and nephritis (IgAV-N), and to evaluate whether B-cell infiltration correlated with clinicopathological variables at kidney biopsy and with short-term renal outcomes. METHODS: Twenty patients with adult-onset IgAV-N and 10 control patients with thin basement membrane nephropathy (TBMN) were retrospectively examined. The lymphatic organization was graded based on B-cell infiltration and was classified into 4 groups: 0-T cells without B cells, 1-scattered B and T cells, 2-clustered B and T cells, and 3-nodular compartmentally arranged B- and T-cell aggregates, equivalent to tertiary lymphoid tissue (TLT). RESULTS: The B-cell infiltration grade was significantly higher in patients with IgAV-N than in patients with TBMN, and no age differences were observed. The B-cell infiltration grade in patients with IgAV-N was significantly correlated with age, serum IgA level, renal dysfunction, and tubulointerstitial injury parameters, but was not correlated with duration after purpura or glomerular injury parameters. Most patients with IgAV-N were treated with corticosteroids. The proteinuria level was significantly decreased, but renal function was not improved in 12 patients after the 24-month follow-up compared with the values at baseline. The B-cell infiltration grade was significantly correlated with renal dysfunction after 24 months of follow-up. CONCLUSIONS: The B-cell infiltration grade in patients with IgAV-N was associated with renal dysfunction and tubulointerstitial injuries but not with glomerular injury parameters. B-cell infiltration and TLT might have a pathologically significant role in irreversible renal dysfunction in patients with early phase adult-onset IgAV-N.

IgA vasculitis with transient glomerular hematuria, diarrhea, and pericarditis following COVID-19 mRNA vaccination in a young patient with possible pre-existing ulcerative colitis.

Exacerbations or de novo autoimmune/autoinflammatory disease have been reported after COVID-19 vaccination. A young male presented with cutaneous IgA vasculitis with glomerular hematuria, diarrhea and pericarditis following his second COVID-19 mRNA vaccination. He also showed positivity for proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) and anti-cardiolipin antibody. Skin biopsy was compatible to IgA vasculitis. His purpura subsided and hematuria spontaneously disappeared. Treatment with anti-inflammatory medications and prednisolone resolved the pericarditis. He had a history of persistent diarrhea, and colonic biopsies showed possible ulcerative colitis without vasculitis. Kidney biopsy after prednisolone therapy revealed minor glomerular abnormalities without any immune reactants and did not show vasculitis. After prednisolone treatment, PR3-ANCA decreased in a medium degree despite of improvement of symptoms and inflammatory data, suggesting that his PR3-ANCA may be associated with ulcerative colitis. The cause of the transient glomerular hematuria was unclear, however, it might be caused by focal glomerular active lesions (glomerular vasculitis) due to vaccine-induced IgA vasculitis with nephritis. This case highlights that COVID-19 mRNA vaccination can activate multiple autoimmune/autoinflammatory systems. The conditions might help us better understand the mutual mechanisms of the relevant disorders.

Selenium Associates With Response to Erythropoiesis-Stimulating Agents in Hemodialysis Patients.

Introduction: Impaired response to erythropoiesis-stimulating agents (ESAs) is associated with increased mortality in patients with end-stage kidney disease. However, the underlying mechanisms are not fully elucidated. Accumulating data reveal that selenium (Se), a trace element, plays a key role in stress erythropoiesis and erythrocyte homeostasis. We evaluated the relationship between serum Se levels and the response to ESAs in hemodialysis patients. Methods: In this cross-sectional study, we determined serum Se levels in 173 hemodialysis patients. We analyzed the association of serum Se with ESA responsiveness, as defined by ESA resistance index. Results: Of the study participants, 50% had lower Se levels than the population-based reference values. We found that serum Se levels were significantly and inversely correlated with erythropoiesis resistance index (ERI) but not transferrin saturation (TSAT) or ferritin levels. Multiple regression analyses confirmed the association between Se levels and ESA hyporesponsiveness, independently of other known factors, such as iron status, being female, and dialysis vintage (ß = -0.11, P < 0.001). When patients were divided according to Se levels and iron status, both low serum Se (<10.5 µg/dl) and iron deficiency significantly affected the response to ESA. Conversely, serum Se levels were significantly different among groups when patients were divided according to ERI quartiles. The association of low serum Se with ESA hyporesponsiveness persisted after adjustment of confounding variables. Conclusion: Serum Se levels are associated with the response to ESAs and can predict ESA resistance independently of iron status in Japanese hemodialysis patients. These data open the possibility to test whether Se supplementation reduces ESA demand.

A Patient with Acute Kidney Injury Associated with Massive Proteinuria and Acute Hyperuricemia after Epileptic Seizures.

A 25-year-old man presented with acute kidney injury (AKI), massive proteinuria and hyperuricemia after epileptic seizures. His AKI improved along with the disappearance of proteinuria after corticosteroid treatment. A kidney biopsy revealed no significant glomerular abnormalities, but varying degrees of tubular injury, such as proximal tubular simplification, mild distal tubular proliferation, and Tamm-Horsfall protein-like material accumulation with extravasation into the interstitium, were noted. A further analysis revealed the intratubular depositions of uric acid crystals, indicating the involvement of acute uric acid nephropathy associated with seizures. Our patient's condition is rare, and the clinicopathological aspects of the diagnostic challenges are discussed.

Emergence of proteinase 3-antineutrophil cytoplasmic antibody-associated glomerulonephritis with mesangial immune deposition during the clinical course of IgG λ monoclonal gammopathy of uncertain significance.

Patients with monoclonal gammopathy of uncertain significance (MGUS) is sometimes associated with renal diseases, usually due to the deposition of secreted monoclonal immunoglobulin or a fragment thereof, a condition which is defined as monoclonal gammopathy of renal significance. Patients with MGUS appear to be at increased risk for various autoimmune conditions. We report the case of a 68-year-old man developed nephritic syndrome and mild renal insufficiency during the course of IgG λ MGUS. Laboratory findings showed hypocomplementemia, cryoglobulinemia, proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) positivity and monoclonal proteins (λ light chain and λ-Bence-Jones protein) in the urine. A kidney biopsy revealed crescentic glomerulonephritis with mesangial immune deposits without paraproteins. Treatment with prednisolone for ANCA-associated glomerulonephritis, normalized urinalysis and decreased PR3-ANCA but MGUS persisted. This is a rare case of PR3-ANCA-associated glomerulonephritis with comorbid IgG λ MGUS with various pathological paraproteins. We highlight it as a clinical example with diagnostic and therapeutic implications.

A Young Patient with Microscopic Polyangiitis Requiring Hemodialysis with Complications of Repeated Episodes of Posterior Reversible Encephalopathy Syndrome Probably Due to Different Etiologies.

A young woman with microscopic polyangiitis (MPA) requiring hemodialysis showed repeated posterior reversible encephalopathy syndrome (PRES) with spatiotemporal multiple lesions over a period of two months. The first PRES episode with confusion and the second PRES episode with vertigo and nausea were caused by MPA, hypertension and renal failure. These symptoms were improved by the reinforcement of MPA treatment and blood pressure management. The third PRES episode with nausea, headache, seizure and visual changes was induced by rituximab infusion and hypertension. The PRES was improved with blood pressure and convulsant management. These conditions are challenging to diagnose and treat.

Characterization of pendrin in urinary extracellular vesicles in a rat model of aldosterone excess and in human primary aldosteronism.

Pendrin is a Cl-/HCO3- exchanger selectively present in the intercalated cells of the kidney. Although experimental studies have demonstrated that pendrin regulates blood pressure downstream of the renin-angiotensin-aldosterone system, its role in human hypertension remains unclear. Here, we analyzed the quantitative changes in pendrin in urinary extracellular vesicles (uEVs) isolated from a total of 30 patients with primary aldosteronism (PA) and from a rat model of aldosterone excess. Western blot analysis revealed that pendrin is present in dimeric and monomeric forms in uEVs in humans and rats. In a rodent model that received continuous infusion of aldosterone with or without concomitant administration of the selective mineralocorticoid receptor (MR) antagonist esaxerenone, pendrin levels in uEVs, as well as those of epithelial Na+ channel (ENaC) and Na-Cl-cotransporter (NCC), were highly correlated with renal abundance. In patients with PA, pendrin levels in uEVs were reduced by 49% from baseline by adrenalectomy or pharmacological MR blockade. Correlation analysis revealed that the magnitude of pendrin reduction after treatment significantly correlated with the baseline aldosterone-renin ratio (ARR). Finally, a cross-sectional analysis of patients with PA confirmed a significant correlation between the ARR and pendrin levels in uEVs. These data are consistent with experimental studies showing the role of pendrin in aldosterone excess and suggest that pendrin abundance is attenuated by therapeutic interventions in human PA. Our study also indicates that pendrin analysis in uEVs, along with other proteins, can be useful to understand the pathophysiology of hypertensive disorders.

Renal Involvement as Rare Acute Tubulointerstitial Nephritis in a Patient with Eosinophilic Disorder Treated with Early Add-on Administration of Mepolizumab.

A 39-year-old man presented with peripheral eosinophilia, pulmonary eosinophilic infiltrate, and renal failure due to acute tubulointerstitial nephritis (TIN). He had experienced childhood asthma and was negative for anti-neutrophil cytoplasmic antibody (ANCA). He was tentatively diagnosed with ANCA-negative eosinophilic granulomatous polyangiitis (EGPA) or idiopathic hypereosinophilic syndrome (HES). Renal involvement of isolated TIN with eosinophil infiltration is rare in EGPA and HES and does not seem to have a good prognosis in the literature. However, his condition improved well with corticosteroids and mepolizumab. The revised classification of EGPA based on the etiology should dictate the proper treatment in suspected EGPA patients with nonsystemic vasculitis.

A Ruptured Jejunal Arterial Aneurysm in a Young Woman Undergoing Chronic Hemodialysis Due to Myeloperoxidase-antineutrophil Cytoplasmic Antibody-associated Vasculitis.

A 21-year-old woman was admitted to our hospital because of massive intestinal bleeding. She started hemodialysis due to myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at 18 years of age. Her ANCA titers remained stable; however, her C-reactive protein increased on 5 mg/day prednisolone before admission. Computed tomography angiography revealed a ruptured jejunal arterial aneurysm. Transcatheter arterial embolization, blood transfusion and the reinforcement of steroid therapy resolved her symptoms of AAV. Our case of a young patient with AAV and medium-sized arterial vasculitis is rare and emphasizes that the ANCA titer does not always rise, especially in patients with nonrenal vasculitis flare-ups.

Pyuria without Casts and Bilateral Kidney Enlargement Are Probable Hallmarks of Severe Acute Kidney Injury Induced by Acute Pyelonephritis: A Case Report and Literature Review.

The patient was a 38-year-old man who had experienced nausea and fever for a few days and presented with back pain, oliguria, and pyuria, suggesting acute pyelonephritis (APN). He showed acute kidney injury (AKI) with bilateral kidney enlargement and was using nonsteroidal anti-inflammatory drugs (NSAIDs). AKI-induced by APN was confirmed by kidney biopsy. The AKI was successfully treated with antibiotic therapy. A search of the relevant literature for reports on histopathologically-proven APN-induced severe AKI revealed that the key characteristics were bilateral kidney enlargement with pyuria without casts. Oligoanuria was frequently associated with APN-induced severe AKI, and NSAID use may be a possible risk factor. Prompt antibiotic treatment based on the clinical characteristics of APN-induced AKI can improve the renal outcome.

Trehalose itself plays a critical role on lipid metabolism: Trehalose increases jejunum cytoplasmic lipid droplets which negatively correlated with mesenteric adipocyte size in both HFD-fed trehalase KO and WT mice.

BACKGROUND: Trehalose is a functional disaccharide that has anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Trehalase hydrolyzes trehalose in the small intestine into two glucose molecules. In this study, we investigated whether trehalose can suppress adipocyte hypertrophy in mice in the presence or absence of trehalase. METHODS: Trehalase knockout (KO) mice and wild-type (WT) mice were fed a high fat diet (HFD) and administered water with 0.3% (w/v) or without trehalose for 8 weeks. At the end of the experimental period, mesenteric adipose tissues and the small intestine were collected and the adipocyte size and proportion of cytoplasmic lipid droplets (CLDs, %) in jejunum epithelium were measured by image analysis. RESULTS: Trehalose treatment was associated with suppressed adipocyte hypertrophy in both trehalase KO and WT mice. The rate of CLDs in the jejunal epithelium was increased in both trehalase KO and WT mice given water containing trehalose relative to untreated control mice. There was a negative correlation between jejunal epithelial lipid droplet volume and mesenteric adipocyte size. Chylomicron-TG tended to be decreased in both trehalose-treated trehalase KO and WT mice. Addition of trehalose to differentiated Caco-2 cells in vitro increased intracytoplasmic lipid droplets and decreased secretion of the chylomicron marker ApoB-48. Moreover, the jejunal epithelium containing lipid droplets falled into the intestinal lumen, and triglyceride (TG) levels in feces tended to be higher in the KO/HFD/Tre group than in the KO/HFD/Water group. Since then, the accumulation of CLDs has been reported to suppress CM secretion, and along with our results, the effect of trehalose to increase jejunum CLDs may induce adipocyte hypertrophy. CONCLUSIONS: The suppression of adipocyte hypertrophy in the presence and absence of trehalase indicates that trehalose mediates effects prior to being hydrolyzed into glucose. In both trehalase KO and WT mice, trehalose treatment increased the rate of CLDs in jejunal epithelium, reduced chylomicron migration from the intestinal epithelium to the periphery, and suppressed adipocyte hypertrophy. Thus, trehalose ingestion could prevent metabolic syndrome by trapping fat droplets in the intestinal epithelium and suppressing rapid increases in chylomicrons.

Continuous intake of Trehalose induces white adipose tissue Browning and Enhances energy metabolism.

BACKGROUND: Trehalose is well known as a functional disaccharide with anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Recently, a new type of adipocyte beige cells, involved in so-called white adipocyte tissue (WAT) browning, has received much attention as a target for adaptive thermogenesis. To clarify the relationship between adipocyte hypertrophy suppression and beige cells involved in thermogenesis, we examined the effect of trehalose on the changes in beige adipocytes in mice under normal dietary conditions. METHODS: Mice fed a normal diet were administered water containing 0.3% (W/V) trehalose for 16 weeks, 0.3% (W/V) maltose, or water without saccharide (controls). Body temperature and non-fasting blood glucose levels were measured every 3 weeks. After 16 weeks of these treatments, mesenteric and inguinal adipose tissues were collected for measuring adipocyte size, counting the number of UCP1 positive cells by image analysis, and preparing mRNA to analyze beige adipocyte-related gene expression. RESULTS: Mice administered a continuous intake of trehalose exhibited a thermogenic ability as represented by an increase in rectal temperature, which was maintained at a relatively high level from 3 to 9 weeks and was significantly higher at 15 weeks in comparison with that of the maltose group. In addition to the reduced hypertrophy of mesenteric and inguinal adipose tissues, the trehalose group showed a significant increase in the rates of beige adipocytes in each WAT in comparison with those of the maltose and the water groups. Interestingly, a negative correlation was found between the mean cell sizes of adipocytes and the rates of beige adipocytes in the WAT. Furthermore, real-time PCR showed that the expression of Cidea and Ucp1 mRNAs, which are markers for beige adipocytes in the inguinal adipose tissue, increased in the trehalose group. CONCLUSIONS: Continuous administration of trehalose to mice fed a normal diet induced WAT browning accompanied by suppression of white adipocyte hypertrophy, elevated body temperature and decreased blood glucose levels, which resulted in enhancement of energy metabolism. Therefore, we propose trehalose as a new type of thermogenic dietary component to prevent obesity by promoting WAT browning.

A Case of Rheumatoid Arthritis Presenting with Renal Thrombotic Microangiopathy Probably due to a Combination of Chronic Tacrolimus Arteriolopathy and Severe Hypertension.

A 51-year-old woman with rheumatoid arthritis presented with mild hypertension 20 months after tacrolimus treatment and developing proteinuria 24 months after the treatment. Tacrolimus was discontinued 27 months after the treatment, followed by heavy proteinuria, accelerated hypertension, and deteriorating renal function without ocular fundus lesions as a clinical sign of malignant hypertension. Renal biopsy revealed malignant nephrosclerosis characterized by subacute and chronic thrombotic microangiopathy (TMA), involving small arteries, arterioles, and glomeruli. Focal segmental glomerulosclerosis, probably secondary to chronic TMA, was identified as a cause of heavy proteinuria. The zonal tubulointerstitial injury caused by subacute TMA may have mainly contributed to deteriorating renal function. The presence of nodular hyalinosis in arteriolar walls was indicative of tacrolimus-associated nephrotoxicity. Together with other antihypertensive drugs, administration of aliskiren stabilized renal function with reducing proteinuria. Owing to the preexisting proteinuria prior to severe hypertension and the complex renal histopathology, we postulated that chronic TMA, which was initially triggered by tacrolimus, was aggravated by severe hypertension, resulting in overt renal TMA.

A Patient with MPO-ANCA-positive IgA Nephropathy Diagnosed with the Clinical Onset of Macrohematuria.

A 21-year-old woman presented with renal dysfunction during macrohematuria. A kidney biopsy revealed IgA nephropathy with a small percentage of crescent formation and macrohematuria-associated tubular injury. Macrohematuria-associated acute kidney injury could explain her renal dysfunction. However, she was seropositive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) and showed fibrin deposition around one arteriole. Corticosteroids and mycophenolate mofetil were administered as for ANCA vasculitis, and the serum creatinine, abnormal urinalysis and MPO-ANCA titer all gradually ameliorated. The presence of extra-glomerular vasculitis, which was probably induced by ANCA, suggested that MPO-ANCA was an exacerbating factor for her prolonged renal dysfunction. This condition has so far only rarely been addressed in ANCA-positive IgA nephropathy.