Protocol for the nationwide registry of patients with polycystic kidney disease: japanese national registry of PKD (JRP).

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are major genetic polycystic kidney diseases that can progress to end-stage kidney disease (ESKD). Longitudinal data on the clinical characteristics associated with clinical outcomes in polycystic kidney disease (PKD), including the development of ESKD and cardiovascular disease (CVD) are lacking in Japan. To address this unmet need the authors are establishing a novel, web-based, Nationwide Cohort Registry Study-the Japanese Registry of PKD (JRP). METHODS: The JRP is a prospective cohort study for ADPKD (aim to recruit n = 1000 patients), and both a retrospective and prospective study for ARPKD (aim to recruit n = 100). In the prospective registry, patients will be followed-up for 10 years every 6 months and 12 months for patients with ADPKD and ARPKD, respectively. Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on April 1, 2024, with recruitment ending on March 31, 2029. (jRCT 1030230618). RESULTS: Data to be collected include: baseline data, demographics, diagnostic and genetic information, radiological and laboratory findings, and therapeutic interventions. During follow-up, clinical events such as development of ESKD, hospitalization, occurrence of extra kidney complications including CVD events, and death will be recorded, as well as patient-reported health-related quality of life for patients with ADPKD. CONCLUSIONS: The JRP is the first nationwide registry study for patients with ADPKD and ARPKD in Japan, providing researchers with opportunities to advance knowledge and treatments for ADPKD and ARPKD, and to inform disease management and future clinical practice.

Nafamostat Mesylate for the Hypercoagulable State of SARS-CoV-2 With Renal Replacement Therapy: A Case Report.

Being a dialysis patient is one of the risks for severe coronavirus disease 2019 (COVID-19) cases. In addition, there have been many reports of coagulation abnormalities in severe COVID-19 cases; these also make dialysis management more difficult. In this study, we report a case of severe COVID-19 in a hemodialysis patient who had coagulation in the dialysis circuit with unfractionated heparin (UFH), which could be managed without intracircuit obstruction when nafamostat mesylate (NM) was used in combination with unfractionated heparin.

Public support for patients with intractable diseases in Japan: impact on clinical indicators from nationwide registries in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Clinical practice guidelines recommend antihypertensive and tolvaptan therapies for patients with autosomal dominant polycystic kidney disease (ADPKD) in Japan. However, tolvaptan therapy may pose an economic burden. The Japanese Ministry of Health, Labour and Welfare supports patients with intractable diseases. This study aimed to confirm the impact of the intractable disease system in Japan on the clinical treatment of ADPKD. METHODS: We analyzed the data of 3768 patients with ADPKD having a medical subsidy certificate from the Japanese Ministry of Health, Labour and Welfare in 2015-2016. The following quality indicators were use: the adherence rate to the 2014 clinical practice guideline for polycystic kidney disease (prescription rates of antihypertensive agents and tolvaptan in this cohort) and the number of Japanese patients with ADPKD nationwide started on renal replacement therapy in 2014 and 2020. RESULTS: Compared with new applications from 2015 to 2016, the prescription rates of antihypertensives and tolvaptan for the indicated patients at the 2017 renewal application increased by 2.0% (odds ratio = 1.41, p = 0.008) and 47.4% (odds ratio = 10.1, p > 0.001), respectively. These quality indicators improved with antihypertensive treatment, especially in patients with chronic kidney disease stages 1-2 (odds ratio = 1.79, p = 0.013) and in those aged < 50 years (odds ratio = 1.70, p = 0.003). The number of patients with ADPKD who were started on renal replacement therapy in Japan decreased from 999 in 2014 to 884 in 2020 in the nationwide database (odds ratio = 0.83, p < 0.001). CONCLUSIONS: The Japanese public intractable disease support system contributes to improvement of ADPKD treatment.

Comparison of the acceptability and safety of molnupiravir in COVID-19 patients aged over and under 80 years.

Background: Molnupiravir is being widely used as a treatment for coronavirus disease 2019 (COVID-19); however, its acceptability and safety in older patients aged ≥ 80 years in real-world clinical practice is not well understood. Methods: We conducted a single-centre retrospective study and assessed the outcome of patients with COVID-19 treated with molnupiravir according to the following criteria: (A) discontinuation rate of molnupiravir; (B) type, frequency, and severity of adverse events; (C) all-cause mortality within 30 days of the diagnosis of COVID-19. Results: Forty-seven patients (46.1%) were aged ≥ 80 years (older patients) and 55 (53.9%) were aged < 80 years (younger patients). There were no significant differences in coexisting diseases and history of vaccination for COVID-19 between older and younger patients. Older patients were significantly more likely to have moderate disease (moderate 1 and 2) according to the Japanese Ministry of Health, Labour and Welfare classification than younger patients. During treatment, 8.5% of older patients and 1.8% of younger patients stopped taking molnupiravir, but the difference was not significant. Adverse events were observed in 39/102 (38.2%) patients. The most common adverse events were diarrhoea (9.8%), exacerbation of coexisting diseases (6.9%), bone marrow suppression (6.9%), liver dysfunction (5.9%), and loss of appetite (4.9%). Most adverse events were minor, ranging from grades 1 to 3. The all-cause mortality rate was 10.8%, and no molnupiravir-related deaths were observed. Conclusions: Molnupiravir treatment is acceptable and safe in older patients with COVID-19 aged ≥ 80 years.

Peritoneal dialysis-related peritonitis caused by Rhodococcus corynebacterioides.

A 57-year-old Japanese man on peritoneal dialysis developed peritoneal dialysis-associated peritonitis caused by Rhodococcus corynebacterioides. After the introduction of peritoneal dialysis, he had experienced four episodes of peritonitis, but the causative organism was not identified in any of episode. When he was hospitalized for the fifth episode of peritonitis, Rhodococcus corynebacterioides was detected in the ascitic fluid. He improved after an intraperitoneal administration of vancomycin (VCM) that was used based on the treatment of peritonitis caused by Corynebacterium spp. However, he then had repeated flare-ups and eventually required the removal of the peritoneal dialysis catheter due to recurrent peritonitis. 16S rRNA gene sequencing is generally needed to positively identify Rhodococcus corynebacterioides. In this case, we were able to rapidly identify the organism by using mass spectrometry and then apply this knowledge to the patient's treatment. To the best of our knowledge, this is the first reported case of peritoneal dialysis-associated peritonitis caused by Rhodococcus corynebacterioides.

Antibiotic prophylaxis for percutaneous renal biopsy: study protocol for a prospective randomized trial.

BACKGROUND: The major complication of renal biopsy is bleeding. Infection is an extremely rare complication of percutaneous renal biopsy, providing sterile techniques are used and bowel perforation does not occur. However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan reported that antibiotic prophylaxis was administered to patients undergoing percutaneous renal biopsy at 61% of 170 adult institutions and 57% of 54 pediatric institutions. The objective of this study is to show the non-inferiority of not administering antibiotic prophylaxis for percutaneous renal biopsy. METHODS: Patients aged ≥15 years who are scheduled to undergo percutaneous renal biopsy are eligible for inclusion in the study. Three hundred and sixty-four patients will be recruited at 6 hospitals. The patients will be randomly assigned at a 1:1 ratio to receive either a single dose of intravenous cefazolin (1 g) or no antibiotic prophylaxis. The primary outcome is the number of patients that exhibit positive urine cultures (>105 colony-forming units/ml) 3 or 4 days after the renal biopsy, or at which point the patients are diagnosed with pyelonephritis until 3 or 4 days after the renal biopsy. The secondary outcomes are the number of patients who are diagnosed with pyelonephritis within 30 days after the renal biopsy, the number of patients who are diagnosed with puncture site infections within 30 days after the renal biopsy, the number of patients who are diagnosed with an infection other than pyelonephritis or a puncture site infection within 30 days after the renal biopsy, and the number of patients who experience cefazolin-induced side effects. DISCUSSION: This randomized controlled trial aims to show the non-inferiority of not administering antibiotic prophylaxis for percutaneous renal biopsy. If this study shows that antibiotic prophylaxis is not needed, it would help to ensure patient safety and prevent the development of antibiotic-resistant bacteria. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000042378 . Registered on 7 Nov 2020.

Safety of Remdesivir for Patients 80 Years of Age or Older with Coronavirus Disease 2019 (COVID-19).

BACKGROUND AND OBJECTIVE: Although older patients with coronavirus disease 2019 (COVID-19) are at the high risk of exacerbation that requires treatment with remdesivir, the safety of this medication is unclear in clinical practice, especially among older patients. We aimed to retrospectively evaluate the safety of remdesivir in older patients with COVID-19 who required hospitalization in our institute. METHODS: We reviewed patients with COVID-19 who were treated with remdesivir at our institute between July 2020 and May 2021. We defined older patients as those aged 80 years or older at admission; all other patients were defined as younger patients. We evaluated the safety of remdesivir by examining the incidence of discontinuation of remdesivir treatment because of adverse events and the incidence of any adverse events. RESULTS: A total of 80 patients were included in this study. Compared with younger patients, fewer older patients were treated with remdesivir for more than 5 days: 4 (15.4%) vs 23 (42.6%). Discontinuation of remdesivir because of adverse events occurred in one older patient (3.9%) and four younger patients (7.4%) [p > 0.99]. Remdesivir-induced liver dysfunction was the most frequent adverse event, which occurred in 29 (36.3%) patients. There were no significant differences in the incidence of remdesivir-induced liver dysfunction, renal dysfunction, and fatigue. CONCLUSIONS: The safety of remdesivir was suggested to be comparable between patients older than 80 years of age and patients younger than 80 years of age. The results of this study may encourage the administration of remdesivir to this older patient group.

Acute rhabdomyolysis in a young woman with moderate COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having serious medical, social, and economic impacts worldwide. COVID-19 may lead to a variety of complications, including rhabdomyolysis. Although rhabdomyolysis is a rare complication, it can lead to severe kidney damage. Recent studies suggest that rhabdomyolysis caused by SARS-CoV-2 is more common in middle-aged and older men with severe COVID-19. Herein we report a case of rhabdomyolysis in a young woman with moderate COVID-19. She had a habit of muscle training. She presented with moderate COVID-19 and acute rhabdomyolysis that required a large volume of fluid infusion in addition to dexamethasone and remdesivir. Clinicians should pay attention to the development of rhabdomyolysis in patients with COVID-19, especially those with a habit of strenuous exercise or muscle training, even if they are young and have moderate COVID-19.

Nivolumab-associated glomerular endothelial injury in a patient with gastric cancer.

A 68-year-old male with gastric cancer was treated with tegafur/gimeracil/oteracil and oxaliplatin for 6 months. Thereafter, he was treated with paclitaxel and ramucirumab for 3 months. However, neither regimen had much effect. Thus, he was treated with nivolumab for 2 months, but he developed proteinuria, microhematuria, and an acute kidney injury. A kidney biopsy revealed occasional swollen endothelial cells and proliferating mesangial cells. Few abnormal findings were seen in the tubules or interstitial tissue. Immunofluorescent staining showed segmental immunoglobulin A and complement component 3 deposition, in the mesangial area. Electron microscopy showed a small amount of electron-dense deposits in the paramesangial area and swollen endothelial cells. Mesangial interposition, the loss of endothelial cell fenestration, and subendothelial edema were also observed. Furthermore, foot process effacement and villous transformation of epithelial cells were noted. After the discontinuation of nivolumab, the patient's renal function gradually improved, and his proteinuria disappeared. Nivolumab treatment was restarted at that time because of cancer progression; however, it was ineffective. No occult blood was detected from 7 months after the administration of the last dose of nivolumab. This is a unique case, in which a kidney biopsy revealed evidence of nivolumab-associated glomerular endothelial injury.

Successful Sodium Level Correction with a 3% Saline Bolus before Intermittent Hemodialysis for a Patient with Severe Hyponatremia Accompanied by Acute Kidney Injury.

A 60-year-old man presented to the emergency department with lightheadedness. He had severe hyponatremia (109 mEq/L) complicated by acute kidney injury (AKI) (serum creatinine: 9.08 mg/dL). Because he was somnolescent, his hyponatremia was initially treated by administering a 130-mL bolus of 3% saline 2 to 5 times per day for 5 days. He subsequently underwent intermittent hemodialysis without any neurological problems. Previous reports have described patients with hyponatremia and AKI being treated with continuous renal replacement therapy. However, our strategy might be a feasible, low-cost treatment strategy of treating patients with hyponatremia and AKI who do not require immediate hemodialysis.

Treatment for renal anemia and outcomes in non-dialysis patients with chronic kidney disease: the current status of regional medicine according to the Kyoto Fushimi Renal Anemia (KFRA) study.

BACKGROUND: The baseline data obtained in the CKD-JAC demonstrated that insufficient treatment was being provided for renal anemia by institutions specializing in renal disease. The objective of this study was to investigate the status of treatment for renal anemia, including renal/cardiovascular outcomes and mortality, at regional medical facilities since the development of long-acting erythropoiesis-stimulating agents (LA-ESA). METHODS: Non-dialysis outpatients with chronic kidney disease and renal anemia were eligible. Anemia was treated based on the clinical condition of each patient and targeted hemoglobin (Hb) levels. RESULTS: A total of 283 patients from 21 institutions were enrolled and followed up for a maximum of 3 years. A doubling of the serum creatinine level was observed in 89 patients, and renal replacement therapy was initiated in 57 patients. Multivariate Cox regression analysis revealed that a lower mean Hb level (mHb) and receiving fewer frequency of ESA during the follow-up period were independent determinants of the composite renal outcome and overall mortality. During the follow-up period, the percentages of patients with mHb of 10-10.9 g/dL and ≥ 11 g/dL were increased. Similar trends were seen regardless of whether the patients were treated by nephrologists or non-nephrologists. The frequency of ESA treatment was increased among the patients treated by non-nephrologists; however, it was much lower than nephrologists. CONCLUSION: This study demonstrated that, in the era of LA-ESA treatment, higher Hb levels are associated with reduced composite renal outcomes at regional medical facilities. The importance of renal anemia management should be highlighted, even among non-nephrologists.

Idiopathic immune complex-mediated tubulointerstitial nephritis with hypocomplementemia and neutrophil-rich interstitial infiltrates
.

A 69-year-old man presented with acute kidney injury, hypocomplementemia, antinuclear antibody, and anti-dsDNA antibody. He had no signs of systemic lupus erythematosus or Sjögren syndrome. He had not begun taking any new drugs in the preceding 6 months. Kidney biopsy revealed 13 glomeruli, 3 with global sclerosis. The remaining glomeruli showed slight mesangial proliferation. The interstitial inflammation was extensive, comprising mainly mature lymphocytes and plasma cells, neutrophils, and a few eosinophils. Remarkable granular and diffuse deposition of IgG and C1q was observed along the tubular basement membranes. Electron microscopy showed electron-dense deposits in the tubular basement membrane. Immunohistochemistry showed only 1 - 4 IgG4-positive plasma cells per high-power field and an IgG4/CD138 ratio of ~ 10%. He was treated with oral prednisolone 35 mg/day, and his kidney function gradually improved. This is a unique case that is not consistent with any known disease entities with immune complex-mediated tubulointerstitial nephritis.
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Membranoproliferative glomerulonephritis with unusual deposits of parallel arrangement striated structure: a new pathological entity?
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A 71-year-old male with a past history of lower limb arteriosclerosis obliterans developed nephrotic syndrome and renal dysfunction. Renal biopsy showed diffuse global endocapillary proliferative lesions with infiltration of mononuclear cells and occasional foam cells. An irregular double contour of the glomerular basement membrane and global mild-to-moderate mesangial proliferative lesions were observed, indicating membranoproliferative glomerulonephritis. Congo red staining was negative. Routine immunofluorescence studies showed no obvious immunoglobulin or complement depositions. Electron microscopy showed endocapillary proliferative lesions and infiltration of macrophages with abundant lysosomes. Irregular subepithelial, subendothelial, and mesangial electron-dense deposits were observed in glomeruli. In these electron-dense deposits, parallel arrangement striated structures were detected. All known disease entities with Congo red-negative and immunoglobulin-negative glomerular deposits were pathologically excluded. The glomerular lesion in our case might be a new disease entity.
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Thrombotic microangiopathy associated with cetuximab, an epidermal growth factor receptor inhibitor
.

Cetuximab is a chimeric human-murine monoclonal antibody that binds competitively and with high affinity to the epidermal growth factor receptor (EGFR) and is used to treat advanced squamous cell carcinoma of the head and neck. After receiving a total of six doses of cetuximab, a 72-year-old male presented with pretibial edema, acne-like skin rash, and nephrotic syndrome. The renal biopsy findings revealed features of thrombotic microangiopathy (TMA), with the expansion of the subendothelial zone, reduplication of the glomerular basement, and swelling of the endothelial cells. Nine weeks after the discontinuation of cetuximab, his pretibial edema had disappeared and proteinuria decreased. To our knowledge, this is the first report in which kidney biopsy revealed evidence of TMA due to cetuximab administration. Our report suggests that it may be prudent to monitor patients receiving cetuximab closely for the possible development of nephrotic syndrome.
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Post-infectious acute glomerulonephritis with vasculitis and pulmonary hemorrhage.

An 84-year-old male complained of fever, cough, sputum, and appetite loss. His renal function rapidly worsened, and he had hypoalbuminemia and hypocomplementemia. His condition worsened and C-reactive protein levels were elevated. Vasculitis syndrome was suspected and he was administered 40 mg of prednisolone, although myeloperoxidase antineutrophil cytoplasmic antibody (ANCA), proteinase-3 ANCA and antiglomerular basement membrane antibody tests were negative. His body temperature decreased and fatigue promptly resumed. On renal biopsy, light microscopy revealed endocapillary and extracapillary glomerulonephritis. Vasculitis was detected in interlobular arteries. Immunofluorescence studies revealed granular deposits of C3 and IgG along capillary walls. Electron microscopy revealed dome-shaped small electron-dense granular subepithelial deposits. Acute post-infectious glomerulonephritis was suspected. Although his renal function improved, he developed hemoptysis and was diagnosed with pulmonary hemorrhage. He received methylprednisolone and plasma exchange, and his respiratory status improved gradually. This is an extremely rare case and suggests the importance of considering a differential diagnosis.

Chaga mushroom-induced oxalate nephropathy.

Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms.

Gamma 1-heavy chain deposition disease accompanied by IgG kappa in serum, urine, and bone marrow.

A 32-year-old Japanese woman presented with hypertension, nephrotic syndrome, microhematuria, and severe hypocomplementemia. Her serum creatinine concentration increased from 1.46 mg/dL (129.0 µmol/L) to 3.46 mg/dL (305.8 µmol/L) over 1 month. Renal biopsy revealed Congo red-negative nodular glomerulosclerosis accompanied by mesangial proliferation. There was extensive staining of immunoglobulin (Ig) G in the glomerular and tubular basement membranes and expanded mesangial regions. Staining was negative for IgA, IgM, and kappa and lambda light chains and positive for the gamma 1 IgG subclass. Staining for constant domains of the gamma heavy chains showed a deletion of the first constant domain (CH1). Electron microscopy revealed electron-dense deposits in the glomerular and tubular basement membranes and mesangium. These findings indicated gamma 1-heavy chain deposition disease (HCDD). Serum and urine immunoelectrophoresis revealed an IgG kappa monoclonal band, whereas bone marrow biopsy revealed monoclonal plasmacytosis with positive staining for kappa chains. HCDD associated with kappa light chain is extremely rare. We report the first case of HCDD with IgG kappa detected in the serum, urine, and bone marrow.