Is Podocytopathy Associated with Gross Hematuria after COVID-19 Vaccination in Patients with Immunoglobulin A Nephropathy?

We experienced three cases of a fever and subsequent severe, prolonged gross hematuria after COVID-19 vaccination. A kidney biopsy revealed immunoglobulin A (IgA) nephropathy, and electron microscopy showed two types of podocytopathy (podocyte damage): loss of foot processes from the glomerular basement membrane and foot process effacement. Mesangial interposition was also present in cases 1 and 3 but not in case 2. Podocytopathy is known to be a cause of proteinuria; however, the reactions to COVID-19 vaccination described here suggest that it may also be related to hematuria in IgA nephropathy.

Immunoglobulin G4-related Dacryoadenitis Successfully Treated with Baricitinib.

A 48-year-old woman visited our hospital because of bilateral lacrimal gland enlargement. Her serum immunoglobulin G4 (IgG4) level was high, and positron emission tomography-computed tomography showed significant positive findings in the bilateral lacrimal gland. A biopsy revealed a considerable increase in IgG4/CD138, leading to a diagnosis of IgG4-related dacryoadenitis. The disease did not respond to steroid therapy, so treatment was started with baricitinib because of exacerbation of the original atopic dermatitis and dacryoadenitis after the second dose of the coronavirus disease 2019 (COVID-19) vaccine. Baricitinib was effective for resolving both dermatitis and dacryoadenitis, and steroids were able to be discontinued. The IgG4 level also improved.

A case of bullous pemphigoid and renal disease after dipeptidyl peptidase 4 inhibitor administration.

A 62-year-old man with type 2 diabetes was admitted because of a decrease in estimated glomerular filtration rate from 72 to 17.5 mL/min/1.73 m2 in 10 years and development of widespread bullous skin lesions. His hemoglobin A1c level had been maintained at 6.0-7.0% for 10 years with a dipeptidyl peptidase (DPP)-4 inhibitor. Skin biopsy showed typical bullous pemphigoid, and kidney biopsy showed tubulointerstitial nephritis with eosinophilic infiltration and glomerular endothelial cell proliferation. After discontinuing the DPP-4 inhibitor, skin lesions improved, and renal decline slowed. This case indicates that DPP-4 inhibitors can cause not only skin lesions but also renal disease.

A Classical Phenotype of Fabry Disease with Novel Mutation Found by Kidney Biopsy, A Case Report.

Fabry disease (FD) is a multi-organ disorder caused by a deficiency of alpha-galactosidase (α-GLA) or reduced activity of the enzyme due to mutations in the GLA gene on the X chromosome, making it an X-linked hereditary disease. A 37-year-old man previously diagnosed with sudden deafness and cardiac hypertrophy was referred to our department after an abnormal urine finding during a public health checkup. A renal biopsy revealed characteristic findings, and he was diagnosed with FD with a novel GLA abnormality (c.714dupT (p.I239Yfs*11)). We are currently administering enzyme replacement therapy (ERT) with agalsidase α. This case shows that a novel genetic abnormality in FD can be overlooked for 37 years, even in the presence of typical symptoms. The significance of a renal biopsy in diagnosing FD is emphasized, highlighting the crucial role of nephrologists.  DOI: 10.52547/ijkd.7595.

Dipeptidyl peptidase-4 inhibitor-related renal disease.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used to treat type 2 diabetes (T2D). Lowering blood glucose is expected also to reduce the progression of diabetic nephropathy. We experienced a patient with T2D who achieved good glycemic control with a DPP-4 inhibitor but experienced rapid deterioration of renal function. Therefore, we performed a retrospective study of similar patients treated at our hospital. METHODS: Out of 56 patients with biopsy-proven diabetic nephropathy who underwent native kidney biopsy at Toranomon Hospital from January 2018 through December 2022, we selected 22 patients who had been receiving DPP-4 inhibitors for at least 9 months at the time of kidney biopsy. Of these patients, we evaluated 16 diagnosed with class IIa diabetic nephropathy according to Tervaert's pathologic classification. The yearly estimated glomerular filtration rate (eGFR) slope in the 16 patients was arranged from the highest to the lowest slope. Ten patients with a large eGFR slope had thrombotic microangiopathy (TMA)-like lesions characterized by glomerular endothelial cell proliferation and GBM duplication on kidney biopsy (group A), whereas the remaining 6 patients did not have TMA-like lesions (group B). RESULTS: Group A had a median (interquartile range [IQR]) eGFR of 18.2 (16.2, 26.2) and a yearly median (IQR) eGFR slope of -11.2 (-17.6, -9.2) mL/min/1.73 m2 after of DPP-4 administration, whereas group B had a median (IQR) eGFR of 31.5 (21.9, 34.8) mL/min/1.73 m2 and a yearly median (IQR) eGFR slope of -1.6 (-3.1, -0.3). Renal function declined significantly more rapidly in group A than in group B, and proteinuria was higher in group A than in group B (median [IQR], 3.4 [2.6, 4.4] g/day vs 0.8 [0.4, 1.3] g/day, respectively). Five patients in group A progressed to dialysis during follow-up, but none of the patients in group B did. Median (IQR) hemoglobin A1c was 6.2 % (6.0 %, 6.6 %) in group A and 5.8 % (5.7 %, 6.6 %) in group B. CONCLUSION: DPP-4 inhibitors promote vascular endothelial regeneration, but when this effect occurs in the glomerulus, glomerular endothelial cell proliferation leads to TMA-like lesions, which may cause an increase in proteinuria and rapid decline in renal function.

Pseudohypercreatininemia after surgery for aortic dissection: a case report.

BACKGROUND: Elevated creatinine concentrations often indicate acute renal injury and renal biopsies are considered in this situation. However,pseudohypercreatininemia is potential cause of elevated creatinine concentrations, and invasive interventions should be avoided. CASE PRESENTATION: A 54-year-old woman underwent surgery for descending aortic dissection.Nine days postoperatively, her creatinine concentration increased from 1 mg/dl to 5.78 mg/dl (normal range, 0.47-0.7 mg/dl). Azotemia and hyperkalemia were absent and physical examination findings were unremarkable. Cystatin C concentration was 1.56 mg/l (normal range, 0.56-0.8 mg/l) and pseudohypercreatininemia was suspected. Testing with different reagents showed a creatinine concentration of 0.84 mg/dl. Immunoglobulin (Ig)G was markedly elevated, and creatinine and IgG fluctuated in parallel, suggesting the cause of the pseudohypercreatininemia. IgG4 was also elevated at 844 mg/dl. Immunosuppressive steroid therapy effectively decreased the IgG concentration and resolved the pseudohypercreatininemia. CONCLUSIONS: In cases of elevated creatinine concentration with the presence of abnormal proteins, pseudohypercreatininemia should be considered. We report a rare case of pseudohypercreatininemia caused by polyclonal IgG.

Rationale and design of an investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized trial to evaluate the effects of finerenone on vascular stiffness and cardiorenal biomarkers in type 2 diabetes and chronic kidney disease (FIVE-STAR).

BACKGROUND: The overactivation of mineralocorticoid receptor (MR) plays a key pathological role in the progression of cardiovascular and renal diseases by promoting pro-inflammatory and pro-fibrotic signaling. Recently, it has been found that finerenone, a novel nonsteroidal selective MR antagonist, can robustly improve cardiorenal outcomes in patients with type 2 diabetes (T2D) and a wide spectrum of chronic kidney disease (CKD). However, the mechanisms underlying the cardiorenal benefits of finerenone are poorly understood. Further, whether the clinical benefits are mediated by an improvement in vascular stiffness is not confirmed. Therefore, the current study aims to evaluate the effects of finerenone on vascular stiffness as assessed using cardio ankle vascular index (CAVI) and relevant cardiorenal biomarkers in patients with T2D and CKD. METHODS: The Effects of Finerenone on Vascular Stiffness and Cardiorenal Biomarkers in Type 2 Diabetes and Chronic Kidney Disease (FIVE-STAR) is an ongoing, investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized clinical trial in Japan. Its target sample size is 100 subjects. Recruitment will be performed from September 2023 to July 2024. After obtaining informed consent, eligible participants with T2D and CKD (25 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 90 mL/min/1.73 m2 and 30 mg/g Cr ≤ urinary albumin-to-creatinine ratio [UACR] < 3500 mg/g Cr) will be equally randomized to receive 24-week treatment with either finerenone (starting dose at 10 mg once daily in participants with a baseline eGFR < 60 mL/min/1.73 m2 or at 20 mg once daily in those with a baseline eGFR ≥ 60 mL/min/1.73 m2) or dose-matched placebo. The primary endpoint is the change from baseline in CAVI at 24 weeks. The secondary endpoints are changes from baseline in UACR at 12 and 24 weeks and relevant serum and urinary biomarkers at 24 weeks. As an exploratory endpoint, proteomic analysis using the Olink® Target 96 panels will be also performed. DISCUSSION: FIVE-STAR is the first trial evaluating the therapeutic impact of finerenone on vascular stiffness and relevant cardiorenal biomarkers in patients with T2D and CKD. This study will provide mechanistic insights on the clinical benefits of finerenone based on recent cardiovascular and renal outcome trials. Trial registration Unique Trial Number, NCT05887817 ( https://clinicaltrials.gov/ct2/show/NCT05887817 ) and jRCTs021230011 ( https://jrct.niph.go.jp/latest-detail/jRCTs021230011 ).

Immunoglobulin G4-related Tubulointerstitial Nephritis with Simultaneous Resolution of Plasma Cell Infiltration and Fibrosis after Steroid Treatment.

We performed 3 kidney biopsies in a 71-year-old man. At the first biopsy, we made the diagnosis of immunoglobulin G4 (IgG4)-related interstitial nephritis characterized by the simultaneous presence of IgG4-positive plasma cells and characteristic fibrosis with a bird's-eye pattern. At the second biopsy, rather than finding fibrosis as a post-inflammatory scar, we noted that steroid treatment had caused the simultaneous disappearance of IgG4-positive plasma cells and fibrosis and had restored the normal tubular structure. The third biopsy showed the recurrence of the disease with inflammatory cells accompanied by fibrosis. These findings suggest that IgG4-positive plasma cells and fibrosis occur simultaneously.

Antiphospholipid Syndrome Nephropathy with Acute Thrombotic Microangiopathy after Renal Transplantation.

We experienced a 36-year-old man with lupus nephritis and antiphospholipid syndrome (APS) who received a donor kidney from his father. Twenty-two months after transplantation, at a time of poor adherence to immunosuppressants and warfarin, the patient developed sudden graft loss due to hemolytic uremic syndrome with rapid deterioration of renal function, thrombocytopenia, and hemolytic anemia. A kidney biopsy showed thrombotic microangiopathy (TMA) related to platelet thrombus formation; however, there was no recurrence of lupus and no findings suggestive of post-transplant rejection, so acute TMA associated with APS was thought to be the cause of the graft loss. This case highlights the importance of instructing patients with lupus nephritis to adhere to treatment with warfarin, a therapeutic drug for APS.

Endothelial Damage-dominant Nephritis Related to IgA Vasculitis after 11 Years' Use of Infliximab for Rheumatoid Arthritis.

A 43-year-old Japanese woman with rheumatoid arthritis treated by infliximab and methotrexate for 11 years was admitted for proteinuria and purpura. A kidney biopsy revealed endothelial damage-dominant nephritis with IgA deposition. Infliximab and methotrexate were discontinued, and tocilizumab was started; however, proteinuria persisted. Therefore, tocilizumab was discontinued, and oral prednisolone and methylprednisolone pulse therapy were administered. After 6 months, urinary protein was less than 0.1 g/day, and purpura subsided. To our knowledge, this is the first case of endothelial damage-dominant nephritis related to IgA vasculitis involving the skin and kidney after long-term use of infliximab and methotrexate.

Antiphospholipid Syndrome Nephropathy Related Disease Diagnosed by Assessing Phosphatidylserine-dependent Antiprothrombin Antibodies.

A 42-year-old Japanese woman was admitted for the evaluation of proteinuria. She had a history of four habitual abortions and valvular heart disease, including severe mitral regurgitation and moderate tricuspid regurgitation. A kidney biopsy showed fibrointimal thickening of interlobular arteries, fibrin thrombosis, and associated focal segmental sclerosis. Although the standard test for antiphospholipid (aPL) antibodies was negative, the patient was diagnosed with antiphospholipid syndrome (APS)-related disease by testing for phosphatidylserine dependent anti-prothrombin anticardiolipin antibody, a non-criterial aPL antibody. A kidney biopsy may lead to a diagnosis of APS in patients with negative laboratory test findings for APS.

A case of thrombotic microangiopathy associated with polymyositis.

A 60-year-old Japanese woman with polymyositis (PM) developed hemolytic anemia (hemoglobin of 7.3 g/dL), thrombocytopenia (platelet of 9.1×104/µL), and acute kidney injury (Cre of 4.7 mg/dL) at 14 days after starting steroid therapy. Renal biopsy revealed glomerular endothelial swelling with fibrin thrombi and fragmented erythrocytes in the capillary lumens. Hemolytic uremic syndrome (HUS) with thrombotic microangiopathy (TMA) was diagnosed. Hemodialysis and plasma exchange/plasma transfusion were initiated, but HUS did not subside. After 45 days, the patient died of hemorrhagic respiratory failure. Autopsy showed fibrin thrombi filling the glomerular vascular pole and the small arteries in most glomeruli, resulting in glomerular collapse and glomerular basement membrane (GBM) duplication. Although renal involvement by PM is rare, HUS/TMA should be remembered as one of the serious renal complications of PM.

Radial artery-second dorsal metacarpal vein arteriovenous fistula in the first interdigital space for hemodialysis: Utilization of the most peripheral site and autologous vein in the upper limb - A case report.

INTRODUCTION: The creation of the first arteriovenous fistula (AVF) as far distally in the upper limb as possible is ideal. We developed a new operative technique for creating a radial artery-second dorsal metacarpal vein AVF in the first interdigital space. This technique involves the creation of the AVF using the most peripheral site and autologous vein in the upper limb. CASE PRESENTATION: We herein describe the steps of this technique and its successful performance in a 71-year-old man with end-stage renal disease. DISCUSSION: This technique has several advantages including preserving many future vascular access options and providing a long segment of arterialized vein for cannulation. CONCLUSION: We consider this technique to be a worthwhile option and recommend the use in patients with the proper vessels for the creation of the AVF.

Assessment of estimated glomerular filtration rate in patients with chronic myeloid leukemia following discontinuation of tyrosine kinase inhibitors.

BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically improved survival outcomes in patients with chronic phase chronic myeloid leukemia (CML-CP) and are associated with a manageable safety profile. However, long-term TKI administration can lead to cardiovascular or renal adverse events. One goal in discontinuation of TKIs was reduction of adverse events, but it is unclear whether chronic toxicities are ameliorated as a result. In this study, we evaluated changes in estimated glomerular filtration rate (eGFR) in patients with CML-CP before and after TKI discontinuation. Long-term TKI treatment appears to induce renal toxicity, as eGFR at the time of TKI discontinuation correlated with the duration of TKI treatment (r = - 0.478, p = 0.005). Patients who received imatinib as first-line treatment exhibited lower eGFR levels than those treated with dasatinib or nilotinib, which may be correlated with long-term treatment (p = 0.027). After TKI discontinuation, no significant increases in eGFR were seen either in patients with treatment-free remission (66.8-71.2 ml/min/1.73 m2) or molecular relapse (64.8-68.7 ml/min/1.73 m2, p = 0.666). These data indicate that TKI-induced renal toxicities are associated with long-term TKI treatment, and may be irreversible even following treatment discontinuation.

Use of the Dorsal Vein of the Hand for Arteriovenous Fistula Creation.

A radiocephalic arteriovenous fistula (AVF) in the anatomical snuffbox is the most distal site of AVF in the upper limb. When the cephalic vein distal to the wrist is in poor condition or thrombosed, creating the typical radiocephalic AVF in the distal forearm just proximal to the wrist will likely be considered. However, we have adopted an operative technique for creating a transposed radial artery-dorsal metacarpal vein AVF (RDAVF) in the anatomical snuffbox when possible in such cases. RDAVF is AVF using the most peripheral autologous vein in the upper limb. To our knowledge, the creation of an RDAVF has not been previously reported. We herein describe the steps of the technique and report the successful treatment of a hemodialysis patient who developed occlusion of a radiocephalic AVF in the anatomical snuffbox.

Effects of hydrogen-rich water in a rat model of polycystic kidney disease.

Various factors are considered to be mechanisms of the increase in the sizes of cysts in patients with polycystic kidney disease. Vasopressin is one of the causes, and drinking large volumes of water shows an effect of suppressing an increase in cysts. On the other hand, it is known that hydrogen-rich water reduces oxidative stress and has a good effect on kidney injury. We examined whether drinking large volumes of hydrogen-rich water affected the increase in the sizes of cysts. Forty 5-week-old PCK rats were randomly assigned to four groups: C(Control), purified water; W(Water), water with sugar; H(Hydrogen), hydrogen-rich water; WH(Water+Hydrogen), hydrogen-rich water with sugar. They consumed water from 5 to 15 weeks of age. The intake of water in the groups in which sugar was added to the water (W, WH) significantly increased in comparison to C, but there was no significant change in the serum Creatinine concentration. The kidney weight per body weight in W was significantly decreased in comparison to C. The kidney weights in H and WH were significantly increased in comparison to W. There were no significant differences in the ratio of the cross-sectional area of the cysts to the whole area among the groups. This experiment showed that the effect of drinking large volumes of hydrogen-rich water was not significantly different from that of normal water, in terms of preventing an increase in the size of cysts in PCK rats. However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period.

A one-sheath inverse method in vascular access intervention therapy for hemodialysis patients.

INTRODUCTION: Vascular access intervention therapy (VAIVT) is an essential interventional therapy in the field of hemodialysis therapy that allows for the long-term vascular access functionality to be maintained. The venous approach is often performed in VAIVT for arteriovenous fistula. When lesions are present on the upstream and downstream sides from the approach site, it is likely that two sheaths will be inserted from two facing punctures. However, we have adopted a one-sheath inverse method using a guidewire in such cases. CASE PRESENTATION: We herein describe the steps of the technique that we have performed and report the successful treatment of a 77-year-old woman who developed arteriovenous fistula failure. DISCUSSION: To the best of our knowledge, the concrete and detailed technique has not been reported in the English literature to date. The merit of the technique is that it allows VAIVT to be performed using one sheath with one approach site in cases in which lesions are present on the upstream and downstream sides from the approach site. The other benefits include pain reduction, a shortened operation time, and reduced costs. Because vascular access location is usually superficial, the technique can be utilized with relative ease. CONCLUSION: A one-sheath inverse method is useful. We hope that the technique will be more widely recognized, allowing the technique to be applied to more cases.

Restoration of Autologous Arteriovenous Fistula by Removal of the Occluded Short Venous Part and Venovenous End-To-End Anastomosis in a Hemodialysis Patient.

Standard salvage procedures for occuluded autologous arteriovenous fistula (AVF) in a hemodialysis patient are endovascular and/or surgical therapy. When endovascular therapy and thrombectomy prove unsuccessful, it is most likely that creating a new AVF or arteriovenous graft will be considered. However, if the occuluded venous part is short, we have adopted an operative technique for repair of AVF by removal of the occluded short venous part and venovenous end-to-end anastomosis. To our knowledge, the efficacy and clinical course of restoration of AVF by the technique have not been reported to date. Here, we describe the technique and report the successful treatment of a hemodialysis patient who developed AVF occlusion.

Thyroid function in patients on continuous ambulatory peritoneal dialysis in comparison with chronic kidney disease
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BACKGROUND/METHODS: Thyroid function was evaluated in 14 Japanese patients on continuous ambulatory peritoneal dialysis (CAPD) with end-stage renal disease compared with 11 chronic kidney disease (CKD) stage 1+2 patients (glomerular filtration rate ≥ 60 mL/min/1.73m2). RESULTS: The serum free triiodothyronine (fT3) (2.2 ± 0.3 pg/mL, p < 0.05) levels were lower, and the rate of low triiodothyronine (T3) syndrome was higher (4 of 13 cases, 30.8%) in the CAPD patients than in the CKD stage 1+2 patients (1 of 10 cases, 10.0%, respectively) or the 57 age-matched healthy controls. The serum thyroglobulin (Tg) levels were significantly higher in the CAPD patients (39.7 (13.4 - 178.0) ng/mL) than in the CKD stage 1+2 patients (9.9 (5.5 - 28.8) ng/mL, p < 0.05). High serum Tg levels (> 30 ng/mL) were observed in 66.7% of the CAPD patients. CONCLUSION: The finding from our study suggested the deterioration of thyroid function with higher prevalence of low T3 syndrome in the CAPD patients. Although speculation as to the reasons for this would be unwise at this point, we did note that the serum Tg levels were very high in the CAPD patients.
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