Associations Between Dietary Potassium Intake From Different Food Sources and Hyperkalemia in Patients With Chronic Kidney Disease.

OBJECTIVE: Previous studies reported mixed results on associations between dietary potassium intake and hyperkalemia in patients with chronic kidney disease (CKD). This study investigated the association between potassium intake from different food sources and hyperkalemia in patients with non-dialysis-dependent CKD. METHODS: A total of 285 patients were recruited at a university hospital and 2 city hospitals in Tokyo. Dietary potassium intake was estimated by a validated diet history questionnaire. Associations of potassium intake from all foods and individual food groups with serum potassium were examined by multivariable linear regression among potassium binder nonusers. An association between tertile groups of potassium intake and hyperkalemia, defined as serum potassium ≥5.0 mEq/L, was evaluated by multivariable logistic regression. RESULTS: Among 245 potassium binder nonusers, total potassium intake was weakly associated with serum potassium (regression coefficient = 0.147, 95% confidence interval (CI): 0.018-0.277), while an association with hyperkalemia was not observed (first vs third tertile: adjusted odds ratio = 0.98, 95% CI: 0.29-3.26). As for food groups, potassium intakes from potatoes, pulses, and green/yellow vegetables were positively associated with serum potassium. Patients in the highest tertile of potassium intake from potatoes had higher odds of hyperkalemia as compared to those in the lowest tertile (adjusted odds ratio = 4.12, 95% CI: 1.19-14.34). CONCLUSION: Total potassium intake was weakly associated with serum potassium, but not with hyperkalemia. Potassium intake from potatoes was associated with hyperkalemia. These findings highlight the importance of considering food sources of potassium in the management of hyperkalemia in CKD.

Relationship between dietary fiber to carbohydrate ratio and mortality risk in US adults: NHANES 2007-2018.

BACKGROUND AND AIMS: The evidence is inconsistent regarding associations between relative proportions of macronutrient intake and disease risk, potentially due to limitations in accounting for differential effects of simple sugars and dietary fiber, grouped as "carbohydrates." We examined the association between the ratio of dietary fiber to carbohydrate intake (FC-R) measure, the relative proportion of macronutrients, and mortality risk in a nationally representative sample of U.S. adults. METHODS AND RESULTS: We performed a retrospective cohort study, using data from the National Health and Nutrition Examination Survey in 2007-2018 and linked mortality data among 15,789 adults aged ≥40 years. We categorized participants into three groups by tertile cutpoints of FC-R, and by percent calories from carbohydrate (<45 %, 45-65 %, and >65 %). Cox proportional hazards regression was performed to estimate hazard ratios (HR) for all-cause mortality with 95 % confidence intervals (95 % CI), adjusting for demographic, health history, and lifestyle factors. During a median follow-up of 6.5 years, 2044 deaths were observed. Compared to the low FC-R group, higher FC-R groups showed a reduction in mortality risk after adjusting for potential confounders (high vs low: HR = 0.71, 95 % CI = 0.62-0.83). The association persisted in those consuming 45-65 % and >65 % of calories from carbohydrate, while the association was attenuated in those with <45 % of calories from carbohydrate. Percent calories from carbohydrate showed no association with mortality risk. CONCLUSION: Higher FC-R was associated with lower all-cause mortality risk in adults with moderate to high levels of percent calories from carbohydrate. Mechanisms of the association warrant further investigation.

Rapidly progressive IgA nephropathy with membranoproliferative glomerulonephritis-like lesions in an elderly man following the third dose of an mRNA COVID-19 vaccine: a case report.

BACKGROUND: As messenger RNA (mRNA)-based vaccines for coronavirus disease 2019 (COVID-19) have been administered to millions of individuals worldwide, cases of de novo and relapsing glomerulonephritis after mRNA COVID-19 vaccination are increasing in the literature. While most previous publications reported glomerulonephritis after the first or second dose of an mRNA vaccine, few reports of glomerulonephritis occurring after the third dose of an mRNA vaccine currently exist. CASE PRESENTATION: We report a case of rapidly progressive glomerulonephritis in a patient following the third dose of an mRNA COVID-19 vaccine. A 77-year-old Japanese man with a history of hypertension and atrial fibrillation was referred to our hospital for evaluation of anorexia, pruritus, and lower extremity edema. One year before referral, he received two mRNA vaccines (BNT162b2) for COVID-19. Three months before the visit, he received a third mRNA vaccine (mRNA-1273) for COVID-19. On admission, the patient presented severe renal failure with a serum creatinine level of 16.29 mg/dL, which had increased from 1.67 mg/dL one month earlier, prompting us to initiate hemodialysis. Urinalysis showed nephrotic-range proteinuria and hematuria. Renal biopsy revealed mild mesangial proliferation and expansion, a lobular appearance, and double contours of the glomerular basement membrane. Renal tubules had severe atrophy. Immunofluorescence microscopy showed strong mesangial staining for IgA, IgM, and C3c. Electron microscopy exhibited mesangial and subendothelial electron-dense deposits, leading to a diagnosis of IgA nephropathy with membranoproliferative glomerulonephritis-like changes. The kidney function remained unchanged after steroid therapy. CONCLUSIONS: Although the link between renal lesions and mRNA vaccines remains unclear, a robust immune response induced by mRNA vaccines may play a role in the pathogenesis of glomerulonephritis. Further studies of the immunological effects of mRNA vaccines on the kidney are warranted.

Understanding the Psychological Well-being of Patients With Locked-in Syndrome: A Scoping Review.

Locked-in syndrome (LiS) is a neurological disorder caused by lesions affecting the ventral pons and midbrain and is characterized by loss of physical function, but with perceived consciousness intact. Despite severely limited function, previous studies have shown the quality of life (QoL) in patients to be more positive than naturally assumed by caregivers and relatives. The present review aims to synthesize the broad scientific literature focused on the psychological well-being of LiS patients. A scoping review was performed to synthesize the available evidence on the psychological well-being of LiS patients. Eligible studies included those that target individuals with LiS as the study population, evaluated psychological well-being, and explored the factors related to it. We extracted study population details, type of QoL methods, method of communication, and primary findings from the studies. We summarized the findings categorized into health-related QoL (HRQoL), global QoL, and other tools for assessing psychological status. Across the 13 eligible studies, we observed that patients with LiS had reasonable or similar psychological well-being as the standard based on HRQoL and global QoL assessment. Caregivers and healthcare professionals seem to rate the psychological QoL of LiS patients lower than patients themselves. Studies showed evidence that the longer duration of LiS is a factor that positively affects QoL, and augmentative and alternative communication tools and recovery of speech production showed positive effects as well. Studies reported a range of 27% to 68% of patients experiencing thoughts of suicide and euthanasia. The evidence shows that LiS patients had reasonable psychological well-being. There appear to be differences between patients' assessed well-being and the negative perceptions by caregivers. Response shift and adaptation to disease by patients are considered potential reasons. A sufficient moratorium period and provision of information to support patients' QoL and appropriate decision-making seems necessary.

Thrombocytopenia during avacopan administration: A case report.

Avacopan is a novel C5a receptor antagonist recently approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis. To our knowledge, thrombocytopenia induced by avacopan has not been reported. We report a case of a 78-year-old man with microscopic polyangiitis who developed rapidly progressive glomerulonephritis (RPGN) and vasculitis neuropathy. After developing RPGN, he was treated with prednisolone, which was ineffective. As the dosage of corticosteroids was decreased, he developed impaired dorsiflexion of the left ankle, tingling and numbness in his feet, consistent with vasculitis neuropathy. After a 3-day administration of methylprednisolone, we started avacopan and prednisolone 20 mg/d to reduce the corticosteroid dosage. One week after starting avacopan, platelet counts began to decrease, eventually leading to the cessation of the drug. The possibility of thrombotic microangiopathy and heparin-induced thrombocytopenia was considered unlikely given the clinical course and laboratory studies. After 3 weeks of avacopan cessation, platelet counts began to increase, suggesting avacopan as the most probable cause of thrombocytopenia. Our case highlights the importance of postmarketing surveillance of avacopan to identify its adverse events that were not reported in clinical trials to ensure its safe use. Clinicians should carefully monitor platelet counts when using avacopan.

Utility of a modified Controlling Nutritional Status score in mortality risk assessment of patients on hemodialysis.

PURPOSE: Malnutrition is common among hemodialysis patients. A nutritional index may be important for their prognosis prediction. We examined the use of a modified version of the Controlling Nutritional Status (CONUT) score as a predictor of mortality in hemodialysis patients and investigated whether statin use modified the association. METHODS: We conducted a retrospective cohort study in 1130 adults (mean age 67.7 years, 35.0% women) on maintenance hemodialysis at four outpatient dialysis clinics in Japan. The exposure of interest was modified CONUT scores calculated by one-time data of serum albumin and total cholesterol at baseline, or mean data of these measures using multiple blood test results. The primary outcome was all-cause mortality. We examined the association between modified CONUT groups (low-risk, middle-risk, and high-risk) and mortality using multivariate Cox proportional hazard regression and logistic regression models in overall patients and by statin use. RESULTS: During a median follow-up of 6.6 years, 525 (46.5%) patients died. Analysis using both one-time and mean data showed increased mortality risk in the high-risk modified CONUT score group as compared to the low-risk group (mean data: HR 2.52, 95% CI 1.96, 3.24); when stratified by statin use, the effect appeared stronger among users (mean data: HR 5.84, 95% CI 2.98, 11.44). Strong predictive ability was observed, particularly for mortality risk at 5 year follow-up using mean data (AUC = 0.842). CONCLUSION: Our results suggest that the modified CONUT score may be useful in helping clinicians quickly identify hemodialysis patients with poorer prognosis who may benefit from close monitoring and interventions.

PTRA is useful for renal artery angina by atherosclerotic plaque rupture with unilateral functioning kidney.

We report a case of acute ischemic nephropathy in a patient with severe renal artery stenosis and bradycardia due to sick sinus syndrome. An 83-year-old Japanese woman with a history of hypertension was diagnosed with sick sinus syndrome and scheduled for pacemaker implantation. Four days prior to admission for the procedure, she experienced sudden-onset severe right flank pain that persisted for 1 day. On the day of admission, her serum creatinine level increased from 1.35 mg/dL, measured 2 weeks earlier, to 7.04 mg/dL. Laboratory examinations showed elevated C-reactive protein and lactate dehydrogenase levels. A computed tomography scan showed a severely atrophied left kidney, suggesting that it was non-functioning. Doppler ultrasonography of the right renal artery showed an extended acceleration time, suggesting proximal stenosis. Magnetic resonance imaging showed no enhancement in the proximal portions of the right renal artery, consistent with severe stenosis or occlusion. The patient developed severe bradycardia with lightheadedness; as a result, pacemaker implantation was performed on post-admission day 7. On day 10, digital subtraction angiography revealed diffuse severe stenosis of the right renal artery; intravascular ultrasonography suggested plaque rupture. Percutaneous transluminal renal angioplasty (PTRA) was performed and a drug-eluting stent was placed. On day 11, hemodialysis was performed owing to deteriorating renal function. The patient's renal function dramatically improved shortly thereafter. This case highlights the importance of PTRA for select patients, as it can potentially save some patients from chronic dialysis, and outlines the possible implications of bradycardia in the pathogenesis of ischemic nephropathy.

Membranous nephropathy in a patient with pulmonary tuberculosis infection and lung adenocarcinoma: a case report.

We report a case of membranous nephropathy (MN) in a patient with tuberculosis infection and lung adenocarcinoma. A 50-year-old Filipino woman underwent a renal biopsy for the evaluation of proteinuria and hematuria. Immunofluorescence analysis revealed positive staining of IgG in the glomerular basement membrane and mesangial matrices, while electron microscopy demonstrated the presence of sub-epithelial deposits, suggesting MN. To screen for secondary causes of MN, we conducted a computed tomography (CT) scan of the chest and abdomen, which revealed a ground-glass opacity in the middle lobe of the right lung and an enlarged paraaortic lymph node. A T-SPOT test was positive, suggesting the possibility of a latent tuberculosis infection, as she was asymptomatic. A follow-up chest CT scan showed persistent presence of the ground-glass opacities, suggesting a non-infectious cause. Video-assisted thoracoscopic resection of the middle right lobe and partial resection of the lower right lobe were performed because the possibility of lung cancer could not be excluded. Notably, pathological analysis of the lung revealed adenocarcinoma in the middle lobe and epithelioid granuloma in the lower lobe, suggesting an active tuberculosis infection. One month after surgery, anti-tuberculosis treatment was initiated. Thereafter, her proteinuria, which had increased to 6 g/gCre preoperatively, began to decrease. Five months after surgery, the patient achieved complete remission. The speed of remission suggests that tuberculosis likely played a primary role in the etiology of MN. Our case underscores the importance of screening tests for infections and malignancies in patients with MN, even if suggestive symptoms are absent.

A Novel LMX1B Variant Identified in a Patient Presenting with Severe Renal Involvement and Thin Glomerular Basement Membrane.

We report a case of nail-patella syndrome (NPS) with unusual thinning of the glomerular basement membrane (GBM) associated with a novel heterozygous variant in the LMX1B gene. A 43-year-old female patient with a previous diagnosis of NPS, referred to our hospital for persistent proteinuria, underwent a renal biopsy, which revealed minor glomerular abnormalities. She underwent a second renal biopsy at the age of 56 owing to the presence of persistent proteinuria and decline in serum albumin, meeting the diagnostic criteria for nephrotic syndrome. Light microscopy demonstrated glomerulosclerosis and cystic dilatation of the renal tubules. Notably, electron microscopy revealed unusual thinning of the GBM, which is quite different from typical biopsy findings observed in patients with NPS, characterized by thick GBM with fibrillary material and electron-lucent structures. Comprehensive genetic screening for 168 known genes responsible for inherited kidney diseases using a next-generation sequencing panel identified a novel heterozygous in-frame deletion-insertion (c.723_729delinsCAAC: p.[Ser242_Lys243delinsAsn]) in exon 4 of the LMX1B gene, which may account for the disrupted GBM structure. Further studies are warranted to elucidate the complex genotype-phenotype relationship between LMX1B and proper GBM morphogenesis.

Immunotactoid glomerulonephritis in a patient with cold agglutinins: causal association or mere coincidence?

We report a case of immunotactoid glomerulonephritis (ITG) in a patient with cold agglutinins. An 86-year-old Japanese male with a history of hypertension, dyslipidemia, and gastric malignancy presented to our hospital for the evaluation of proteinuria and hematuria. He had an elevated blood pressure of 200/77 mmHg and edema of the lower extremities. Initial blood test results revealed an impaired renal function (creatinine, 1.37 mg/dL) and hypoalbuminemia (albumin, 2.6 g/dL). His estimated daily urinary protein was 5.89 g/g creatinine, meeting the diagnostic criteria for nephrotic syndrome. The selectivity index for proteinuria indicated low selectivity (0.329). We conducted a renal biopsy to identify the cause of nephrotic syndrome. Immunofluorescence microscopy demonstrated positive staining of IgM, C4, and C1q. Electron microscopy exhibited mesangial expansion with inflammatory cells and a lobular structure, suggesting membranoproliferative glomerulonephritis. Subendothelial deposits containing microtubular structures with a diameter of approximately 30-200 nm were found, concurrent with the criteria for the diagnosis of ITG. Screening for lymphoproliferative diseases and immunological abnormalities revealed a positive direct Coombs test result and the presence of cold agglutinins. Paraproteinemia was absent. The similarities between cold agglutinin disease and ITG, including the production of autoantibodies and involvement of complement pathways, raise the possibility that cold agglutinins played a role in the development of ITG; however, we were unable to prove it due to difficulties in detecting cold agglutinins on renal histology. We discuss the possible implications for pathogenesis considering prior reports on nephrotic syndrome being potentially associated with cold agglutinins.

The utility of portable negative pressure wound therapy in the management of prosthetic dialysis arteriovenous graft infection.

The management of prosthetic dialysis arteriovenous graft infection comprises antibiotic treatment and total or partial excision of infected grafts for infectious source control. Partial excision with graft bypass is an important graft preservation strategy for localized infection but carries a higher reinfection risk. Here, we report a case of prosthetic graft infection that was successfully treated with partial excision, a graft bypass procedure, and a portable negative pressure wound therapy system, PICO, applied to the open wound postoperatively. The combined approach may be a useful strategy that decreases reinfection risk, shortens the length of hospital stay, and preserves graft patency.

Immersion pulmonary edema in a patient on maintenance dialysis: A case report.

Immersion pulmonary edema (IPE) is a rare condition observed in divers. We report a case of a 66-year-old man on maintenance dialysis who developed acute dyspnea and blood-tinged sputum after scuba diving. Vital signs on admission were significant for elevated blood pressure at 209/63 mmHg and hypoxia with an oxygen requirement of 6 L/min. Physical examination was remarkable for bilateral coarse crackles and systolic ejection murmur. Chest radiography revealed bilateral pulmonary edema. Echocardiography showed aortic stenosis and diffuse hypokinesis of left ventricular wall motion. We started bilevel positive airway pressure and administered nitroglycerin and nicardipine to maintain adequate oxygenation and reduce blood pressure. We started hemodialysis and extracorporeal ultrafiltration to remove excess fluid. His dyspnea subsided and oxygen was no longer required on Day 3. His long-standing hypertension, increased afterload due to vasoconstriction induced by cold water, increased capillary pressure due to impaired left ventricular motion and increased preload caused by exertion, and aortic stenosis probably contributed to pulmonary congestion. We propose maintenance dialysis as a novel risk factor for IPE due to its tendency to induce volume overload, increase pulmonary capillary pressure, and increase aortic stenosis risk. Patients on hemodialysis should refrain from diving to prevent this life-threatening condition.

Association between dietary fibre:carbohydrate intake ratio and insulin resistance in Japanese adults without type 2 diabetes.

An easily understandable index that measures the quality of carbohydrate may aid people in adopting dietary habits that improve their glucose tolerance. We aimed to evaluate the relationship between a ratio of dietary fibre to carbohydrate intakes (fibre:carbohydrate ratio (F:C-R)) and glucose tolerance cross-sectionally and longitudinally. Subjects were 190 Japanese men and women without type 2 diabetes (mean age 55·4 years) who participated in a 5-month diet and exercise programme. We compared baseline anthropometric, dietary and metabolic profiles between those with higher F:C-R and those with lower ratios. Multivariable regression analyses were performed to examine the associations between the F:C-R and homoeostasis model of assessment for insulin resistance (HOMA-IR) and HbA1c at baseline and between changes in the F:C-R and changes in HOMA-IR and HbA1c over the 5-month period. At baseline, the higher F:C-R group had significantly lower body weight, lean body mass, fasting insulin level and HOMA-IR as compared with the lower F:C-R group. The two groups had similar intakes of carbohydrate and fat, whereas protein intake was greater in the high F:C-R group. Baseline F:C-R was not significantly associated with HOMA-IR or HbA1c at the beginning of the study in multivariable models. Increases in the ratio during the 5-month programme was associated with reductions in HbA1c (P<0·001). These findings highlight the potential utility of the F:C-R in strategies aimed at type 2 diabetes prevention.

Change in the efficacy of influenza vaccination after repeated inoculation under antigenic mismatch: A systematic review and meta-analysis.

OBJECTIVES: To examine the effects of repeated influenza vaccination on medically-attended influenza (MAI) and acute respiratory illness (ARI) risk according to the antigenic matching between vaccine and circulating virus strains. METHODS: We performed a systematic review and meta-analysis of randomized studies that compared the risk of MAI and ARI between subjects who had been vaccinated for two consecutive seasons (multiple vaccine group) and those who had been vaccinated in the current season and not in the previous season (single vaccine group). RESULTS: Of 1467 articles identified, eight studies covering ten seasons were included in meta-analyses. Six studies assessed efficacy against MAI in children, yielding the risk ratios (RR) of 2.04 (95% CI 1.29-3.22) when circulating strains mismatched vaccine strains, and 0.64 (0.33-1.22) when circulating strains matched vaccine strains. When stratified by vaccine types, the reduced efficacy was significant for live-attenuated influenza vaccine only. Three studies investigated efficacy against ARI in children, with the RR of 0.96 (0.81-1.15). The results on adults and the elderly were scarce. CONCLUSIONS: Influenza vaccine efficacy against mismatch strains was lower in repeatedly vaccinated children as compared with those vaccinated for the current season only. The scarcity of available studies may call for further randomized controlled trials on repeated influenza vaccination.

Kelch-Like Protein 2 Mediates Angiotensin II-With No Lysine 3 Signaling in the Regulation of Vascular Tonus.

Recently, the kelch-like protein 3 (KLHL3)-Cullin3 complex was identified as an E3 ubiquitin ligase for with no lysine (WNK) kinases, and the impaired ubiquitination of WNK4 causes pseudohypoaldosteronism type II (PHAII), a hereditary hypertensive disease. However, the involvement of WNK kinase regulation by ubiquitination in situations other than PHAII has not been identified. Previously, we identified the WNK3-STE20/SPS1-related proline/alanine-rich kinase-Na/K/Cl cotransporter isoform 1 phosphorylation cascade in vascular smooth muscle cells and found that it constitutes an important mechanism of vascular constriction by angiotensin II (AngII). In this study, we investigated the involvement of KLHL proteins in AngII-induced WNK3 activation of vascular smooth muscle cells. In the mouse aorta and mouse vascular smooth muscle (MOVAS) cells, KLHL3 was not expressed, but KLHL2, the closest homolog of KLHL3, was expressed. Salt depletion and acute infusion of AngII decreased KLHL2 and increased WNK3 levels in the mouse aorta. Notably, the AngII-induced changes in KLHL2 and WNK3 expression occurred within minutes in MOVAS cells. Results of KLHL2 overexpression and knockdown experiments in MOVAS cells confirmed that KLHL2 is the major regulator of WNK3 protein abundance. The AngII-induced decrease in KLHL2 was not caused by decreased transcription but increased autophagy-mediated degradation. Furthermore, knockdown of sequestosome 1/p62 prevented the decrease in KLHL2, suggesting that the mechanism of KLHL2 autophagy could be selective autophagy mediated by sequestosome 1/p62. Thus, we identified a novel component of signal transduction in AngII-induced vascular contraction that could be a promising drug target.