A Rare Manifestation of IgG4-Related Disease and Secondary Hypereosinophilic Syndrome: A Case Report.

We report a case of IgG4-related disease with marked eosinophilia. A 79-year-old woman was admitted due to diarrhea, and weight loss. Cervical lymphadenopathy, bilateral submandibular glands swelling, anemia (Hb8.5g/dl), hypereosinophilia (9,750/µL), and elevated serum creatinine (1.57 mg/dL), pancreatic amylase (191 IU/L), and IgG4 (3,380 mg/dL) were found. Diffusion-weighted image on MRI showed high intensity signals inside of both the pancreas and the kidney. The echogram of submandibular glands revealed cobblestone pattern. Kidney biopsy revealed acute tubulointerstitial nephritis. Biopsies of lip, gastrointestinal tract and bone marrow showed infiltration of lymphoplasmacytic cells and IgG4 positive plasma cells (30-67/HPF). Gastrointestinal and bone marrow biopsies also showed eosinophilic infiltration. Adrenal insufficiency, rheumatic disease, tuberculosis, parasite infection, drug induced eosinophilia, and eosinophilic leukemia were all ruled out. We started treatment with 40mg of prednisolone and her general condition rapidly improved. The eosinophil count, serum IgG4, and serum creatinine decreased. We gradually tapered prednisolone and maintained 5mg/day. During the 5 years of treatment, she had no recurrence of the symptom. According to the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease, eosinophils > 3000/µL is one of the exclusion criteria. If we comply this criterion, the diagnosis of IgG4-related disease should be avoided. However, our case fit the diagnostic criteria of type I autoimmune pancreatitis, IgG4-related sialadenitis and global diagnosis of IgG4-related disease. We finally diagnosed our case as IgG4-related disease with secondary hypereosinophilic syndrome. This case suggests that IgG4-related disease with eosinophils > 3000/µL does exist in the real world.

A case of acute kidney injury due to native kidney BK polyomavirus-associated nephropathy in a human T-lymphotropic virus type 1 carrier.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) has become a major cause of kidney dysfunction and graft loss in kidney transplant recipients. On rare occasion, polyomavirus has also been known to affect native kidneys of immunocompromised individuals. Only a small number of opportunistic infections have been reported in the carrier phase of human T-lymphotropic virus type 1 (HTLV-1). This is the first reported case of BKPyVAN in native kidneys of an HTLV-1 carrier. CASE PRESENTATION: A 61-year-old man was referred to our hospital from a primary care physician for work-up and treatment of pneumonia. He was diagnosed with Pneumocystis pneumonia and identified as a HTLV-1 carrier who had not yet developed adult T-cell leukemia (ATL). The pneumonia was successfully treated with sulfamethoxazole-trimethoprim. He had never been diagnosed with any kind of kidney dysfunction. Laboratory investigations showed a serum creatinine of 5.3 mg/dL, and urinary sediment showed cells with nuclear enlargement and inclusion bodies suggesting viral infection. The urinary Papanicolaou stain showed inclusions in swollen, ground-glass nuclei, typical of "decoy cells". Renal biopsy showed degeneration of tubules with epithelial enlargement, vacuolar degeneration, nuclear inclusion bodies, and detachment from the tubular basement membrane. Tubular nuclei showed positive staining positive for simian virus 40 large-T antigen. Polymerase chain reaction tests for BK polyomavirus DNA of both urine and plasma were positive. These findings confirmed a diagnosis of BKPyVAN. Intravenous immunoglobulin therapy did not improve renal function, necessitating maintenance hemodialysis therapy. CONCLUSIONS: BKPyVAN should be considered when acute kidney injury occurs with opportunistic infection. HTLV-1 carriers can develop opportunistic infections even before the onset of ATL.

Risk factor for progression to kidney failure with replacement therapy in elderly patients with chronic kidney disease: A retrospective single-centre cohort study.

BACKGROUND: Although the number of elderly patients with chronic kidney disease (CKD) has increased, few studies have examined their prognosis. METHODS: The study design was a retrospective cohort study at a single centre. We evaluated 301 patients aged ≥75 years old with CKD stage G3a to G5. The primary endpoint was kidney failure with replacement therapy (KFRT) and secondary endpoints were all-cause mortality and annual decline rates of estimated glomerular filtration rate (eGFR). The incidence of KFRT was estimated using the cumulative incidence method considering the competing risk of death. To identify the independent risk factors related to KFRT, multivariate Fine-Gray regression model analysis were performed. RESULTS: The median age of the patients was 79 years and the median eGFR was 24.0 mL/min/1.73 m2 at baseline. Urinary protein was positive in 70% of patients. With a median follow-up of 24.5 months, 35% of the patients developed KFRT and 9% died. Kidney survival significantly decreased according to the CKD stage at baseline. In patients without proteinuria, the cumulative incidence of KFRT increased in CKD stage G5 patients, while in patients with proteinuria, the incidence of KFRT increased from patients with CKD stage G3b. Multivariate Fine-Gray regression model revealed that less aged, CKD stage G5, baseline data such as proteinuria, hypoalbuminemia, hyperphosphatemia, and hyperuricemia were independent risk factors for KFRT. CONCLUSION: Elderly CKD patients with proteinuria need to be carefully monitored even at an early CKD stage because of the risk of developing KFRT.

Association of blood pressure after peritoneal dialysis initiation with the decline rate of residual kidney function in newly-initiated peritoneal dialysis patients.

BACKGROUND: Lower blood pressure (BP) levels are linked to a slower decline of kidney function in patients with chronic kidney disease (CKD) without kidney replacement therapy. However, there are limited data on this relation in peritoneal dialysis (PD) patients. Here we evaluated the association of BP levels with the decline of residual kidney function (RKF) in a retrospective cohort study. METHODS: We enrolled 228 patients whose PD was initiated between 1998 and 2014. RKF was measured as the average of creatinine and urea clearance in 24-hr urine collections. We calculated the annual decline rate of RKF by determining the regression line for individual patients. RKF is thought to decline exponentially, and thus we also calculated the annual decline rate of logarithmic scale of RKF (log RKF). We categorized the patients' BP levels at 3 months after PD initiation (BP3M) into four groups (Optimal, Normal & High normal, Grade 1 hypertension, Grade 2 & 3 hypertension) according to the 2018 European Society of Cardiology and European Society of Hypertension Guidelines for the management of arterial hypertension. RESULTS: The unadjusted, age- and sex-adjusted, and multivariable-adjusted decline rate of RKF and log RKF decreased significantly with higher BP3M levels (P for trend <0.01). Compared to those of the Optimal group, the multivariable-adjusted odds ratios (95% confidence interval) for the faster side of the median decline rate of RKF and log RKF were 4.04 (1.24-13.2) and 5.50 (1.58-19.2) in the Grade 2 and 3 hypertension group, respectively (p<0.05). CONCLUSIONS: Higher BP levels after PD initiation are associated with a faster decline in RKF among PD patients.

Late renal recovery after treatment over 1 year post-onset in an atypical hemolytic uremic syndrome: a case report.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease that leads to end-stage kidney disease if only a poor response to plasma exchanges (PEs) or eculizumab therapy is achieved. CASE PRESENTATION: A 58-year-old Japanese man presented with thrombocytopenia, anemia, and kidney failure requiring dialysis without any underlying disease. A kidney biopsy revealed marked mesangiolysis in all glomeruli, compatible with thrombotic microangiopathy (TMA). Based on the positive anti- factor H antibody and negative result for secondary TMA, we diagnosed him as aHUS. Despite eculizumab administration after eight sessions of PE, neither platelet normalization nor kidney recovery was achieved. Eight months later, we discontinued eculizumab therapy due to anaphylactic reaction. At 15 months after the onset of TMA, his platelet count increased gradually from 40 to 150 × 103/µL with a decreased serum creatinine level and increased urine output, eventually allowing the withdrawal of dialysis therapy. A second kidney biopsy showed mesangial widening compatible with the healing of TMA. CONCLUSIONS: This case indicates that aHUS with PEs and eculizumab therapy has the potential for renal recovery even if over 1 year has passed.

The first case of COVID-19 pneumonia in a hemodialysis patient in Japan.

On 31 December 2019, cases of pneumonia whose cause was later identified as SARS-CoV-2 were detected in Wuhan City, Hubei Province of China, and now COVID-19 has spread worldwide. On March 1, 2020, a 69-year-old Japanese man who had been on hemodialysis for 3 years was diagnosed as having COVID-19 pneumonia and hospitalized at our Medical Center. Pulmonary CT revealed bilateral multiple consolidation with bilateral pleural effusion. Aggressive weight reduction was needed to improve the patient's respiratory condition. Hemodialysis therapy was performed in isolation with hydroxychloroquine administration, but the formation of a dialysis membrane clot forced the withdrawal of dialysis therapy. Changing the dialysis membrane material and anticoagulant enabled the resumption of dialysis therapy, allowing the body weight to correct downward. On the 5th hospitalization day, the patient's fever dropped and he showed improved oxygenation and chest X-ray. He was eventually discharged. The hydroxychloroquine and appropriate fluid management may have contributed to the patient's recovery. Clinicians should pay close attention to avoid dialysis-related problems when treating a patient with COVID-19.

The glucose degradation product methylglyoxal induces immature angiogenesis in patients undergoing peritoneal dialysis.

The accumulation of glucose degradation products (GDPs) can lead to tissue damage in patients with diabetes and those undergoing long-term peritoneal dialysis (PD). Angiogenesis is occasionally observed in the peritoneal membrane of patients undergoing PD, where it is associated with failure of ultrafiltration. To investigate the mechanism underlying the influence of angiogenesis on fluid absorption, we evaluated the effects of accumulation of the glucose degradation product methylglyoxal (MGO) on angiogenesis in vitro, and analyzed the association with angiogenesis in the peritoneal membrane. To this end, we measured the levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in cultured endothelial and smooth muscle cells after administration of MGO. The expression of PDGF-BB mRNA and protein decreased significantly after exposure to MGO, while the expression of VEGF mRNA increased (both P < 0.01). The expression of PDGF-Rß mRNA in cultured smooth muscle cells did not change after administration of MGO, although the expression of VEGF mRNA increased (P < 0.01). We also evaluated the associations between the number of capillary vessels, peritoneal function, and the degree of MGO deposition using peritoneum samples collected from patients undergoing PD. The number of immature capillary vessels was significantly associated with peritoneal dysfunction and the degree of MGO accumulation (both P < 0.01). In conclusion, MGO enhances the production of VEGF and suppresses the production of PDGF-BB, potentially leading to disturbance of angiogenesis in the peritoneal membrane. Accumulation of MGO in the peritoneum may cause immature angiogenesis and peritoneal dysfunction.

Advanced glycation end products are associated with immature angiogenesis and peritoneal dysfunction in patients on peritoneal dialysis.

BACKGROUND: Deposition of advanced glycation end products (AGEs) is frequently found in the peritoneum of patients on peritoneal dialysis (PD). Angiogenesis is also observed in the peritoneum. However, the clinical significance of AGEs and angiogenesis in the peritoneum is not fully understood. We evaluated the maturation of capillary vessels and investigated whether AGEs are associated with angiogenesis and peritoneal function in the peritoneal membrane. METHODS: Peritoneum obtained when PD catheters were removed from 61 patients with PD was analyzed. The peritoneum was immunohistochemically stained with anti-CD34 (for endothelial cells), anti-alpha smooth muscle actin (αSMA) (for pericytes), and anti-AGE antibodies. We defined CD34-positive and αSMA-negative vessels as immature capillary vessels in peritoneal membranes using serial sections. We evaluated the associations between vessel density, peritoneal function (dialysate-to-plasma ratio for creatinine (D/P creatinine)), and the degree of AGE deposition. RESULTS: AGE accumulation in the interstitium was positively associated with the duration of PD (p < 0.01). AGE accumulation in the interstitium and vascular wall was positively correlated with the use of acidic solution (p < 0.05) and the maximum value of D/P creatinine (p < 0.05). AGE accumulation in the vascular wall was significantly associated with immature capillary density (CD34+/αSMA-) in the peritoneum (p < 0.01). Vessel density was not significantly correlated with the last measurement of D/P creatinine (p = 0.126, r = 0.202), However, immature capillary density was positively correlated with the last measurement of D/P creatinine (p < 0.05, r = 0.278). CONCLUSIONS: AGE accumulation is significantly associated with immature angiogenesis and peritoneal dysfunction in patients undergoing PD.

Relative hypophosphatemia early after transplantation is a predictor of good kidney graft function.

BACKGROUND: Phosphate level is a potent independent risk factor for cardiovascular disease and mortality in patients with chronic kidney disease. The association between hypophosphatemia and kidney function in kidney transplant patients is uncertain. METHODS: In total, 90 kidney transplant recipients were divided into two groups: one group of patients with hypophosphatemia and the other group without hypophosphatemia. The recipients with hypophosphatemia were identified as having less than or equal to the lowest quartile of serum phosphate levels at 1-, 3-, and 12-month post-transplant. The cumulative kidney survival rates were calculated for each group using the Kaplan-Meier method, and the adjusted hazard ratio (HR) was calculated using the Cox regression model. RESULTS: The mean age of patients was 47 years and the median follow-up period was 58 months. During the follow-up period, the following results were demonstrated in 90 transplant patients: graft loss (n = 6), mortality (n = 3). According to the Kaplan-Meier analysis results, the patients with hypophosphatemia demonstrated a significantly lower risk of 30% decline in eGFR compared to those without hypophosphatemia at 1- and 3-month post-transplant, but not at 12-month post-transplant. After adjusting for confounding factors, hypophosphatemia at 1- and 3-month post-transplant was an independent predictor of good kidney survival (HR 0.31, 95% CI 0.10-0.82 and HR 0.31, 95% CI 0.07-0.92, respectively). CONCLUSIONS: Our findings suggest that hypophosphatemia during the first 3 months after kidney transplantation was associated with better kidney survival.

Comparison of Suicide Rates Among Asian Americans in 2000 and 2010.

This brief report used the mortality data to separately examine suicide rates of the six largest Asian American groups: Chinese, Filipino, Indian, Japanese, Korean, and Vietnamese. In 2000, Japanese American men (13.8 per 100,000) showed significantly higher suicide rate than Chinese, Indian, and Vietnamese American men (7.3, 4.0, and 6.1 per 100,000), whereas Chinese, Korean, and Japanese women (3.7, 3.9, and 4.3 per 100,000) showed higher suicide rates than Indian women (1.2 per 100,000). In 2010, Korean and Japanese American men (19.9 and 15.7 per 100,000) showed higher suicide rates than men of other Asian groups. Korean and Japanese American women (8.1 and 5.0 per 100,000) showed higher suicide rates than Indian and Filipino American women (1.5 and 1.8 per 100,000). The findings challenge the notion that Asian Americans are at low risk for suicide and underscore the importance of examining ethnic variation in suicide behaviors among Asian Americans.

Inhibition of Large Neutral Amino Acid Transporters Suppresses Kynurenic Acid Production Via Inhibition of Kynurenine Uptake in Rodent Brain.

The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor and N-methyl-D-aspartic acid receptor at endogenous brain concentrations. Recent studies have suggested that increases of brain KYNA levels are involved in psychiatric disorders such as schizophrenia and depression, and regulation of KYNA production has become a new target for treatment of these diseases. Kynurenine (KYN), the immediate precursor of KYNA, is transported into astrocytes via large neutral amino acid transporters (LATs). In the present study, the effect of LATs regulation on KYN uptake and KYNA production was investigated in vitro and in vivo using an LATs inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). In the in vitro study, cortical slices of rat brain were incubated with a physiological concentration of KYN and 3 µmol/L-3 mmol/L BCH. BCH inhibited KYNA production and KYN uptake in a dose-dependent manner, and their IC50 values were 90.7 and 97.4 µmol/L, respectively. In the in vivo study, mice were administered KYN (50 mg/kg BW) orally and BCH (200 mg/kg BW) intravenously. Administration of KYN increased brain KYN and KYNA levels compared with the mice treated with vehicle, whereas additional administration of BCH suppressed KYN-induced elevations in KYN and KYNA levels to 50 and 70 % in the brain. These results suggest that inhibition of LATs prevented the increase of KYNA production via blockade of KYN uptake in the brain in vitro and in vivo. LATs can be a target to modulate brain function by regulation of KYNA production in the brain.

Mouthguard biosensor with telemetry system for monitoring of saliva glucose: A novel cavitas sensor.

We develop detachable "Cavitas sensors" to apply to the human oral cavity for non-invasive monitoring of saliva glucose. A salivary biosensor incorporating Pt and Ag/AgCl electrodes on a mouthguard support with an enzyme membrane is developed and tested. Electrodes are formed on the polyethylene terephthalate glycol (PETG) surface of the mouthguard. The Pt working electrode is coated with a glucose oxidase (GOD) membrane. The biosensor seamlessly is integrated with a glucose sensor and a wireless measurement system. When investigating in-vitro performance, the biosensor exhibits a robust relationship between output current and glucose concentration. In artificial saliva composed of salts and proteins, the glucose sensor is capable of highly sensitive detection over a range of 5-1000µmol/L of glucose, which encompasses the range of glucose concentrations found in human saliva. We demonstrate the ability of the sensor and wireless communication module to monitor saliva glucose in a phantom jaw imitating the structure of the human oral cavity. Stable and long-term real-time monitoring (exceeding 5h) with the telemetry system is achieved. The mouthguard biosensor will be useful as a novel method for real-time non-invasive saliva glucose monitoring for better management of dental patients.

Risk factors for suicidal behaviors among Filipino Americans: a data mining approach.

Filipino Americans have lower suicide rates than other Asian ethnic groups. The present study examined risk factors for suicide ideation and attempt among Filipino Americans with random forest. The data were from the Filipino American Community Epidemiological Study (Takeuchi, 2011). The results showed that the important predictors for suicide ideation were depressive disorder, substance use disorder, and years in the United States. The important predictors for suicide attempt were the number of family relatives and family conflict. Clinicians are advised to investigate familial and cultural factors among Filipino Americans. How family and cultural factors may affect suicidal behaviors were further discussed.

Brain atrophy in peritoneal dialysis and CKD stages 3-5: a cross-sectional and longitudinal study.

BACKGROUND: Brain atrophy has been reported in patients with end-stage renal disease receiving hemodialysis, although its mechanism is unknown. However, little is known regarding brain atrophy in patients receiving peritoneal dialysis (PD). Therefore, we examined brain volume and its annual change over 2 years in PD patients compared with patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). STUDY DESIGN: Cross-sectional and longitudinal cohort. SETTING & PARTICIPANTS: 62 PD patients and 69 patients with NDD-CKD with no history of cerebrovascular disease who underwent brain magnetic resonance imaging (MRI) were recruited in a cross-sectional study. Among them, 34 PD patients and 61 patients with NDD-CKD, who underwent a second brain MRI after 2 years, were recruited in a longitudinal study. PREDICTOR: PD therapy versus NDD-CKD. OUTCOMES & MEASUREMENTS: T1-weighted magnetic resonance images were analyzed. Total gray matter volume (GMV), total white matter volume (WMV), and cerebrospinal fluid space volume were segmented, and each volume was quantified using statistical parametric mapping software. Normalized GMV and WMV values were calculated by division of GMV and WMV by intracranial volume to adjust for variations in head size. We compared normalized GMV and normalized WMV between PD patients and patients with NDD-CKD in the cross-sectional study and the annual change in normalized GMV in the longitudinal study. RESULTS: In the cross-sectional study, normalized GMV, which was correlated inversely with age, was lower in PD patients than in patients with NDD-CKD. However, normalized WMV, which was not correlated with age, was comparable between the groups. Annual change in normalized GMV was significantly higher in PD patients than in patients with NDD-CKD. These differences remained significant even after adjustment for potential confounding factors. LIMITATIONS: A short observation period and high dropout rate in the longitudinal study. CONCLUSIONS: Decline in normalized GMV is faster in PD patients than in patients with NDD-CKD.

Probable light- and heavy-chain deposition disease in a patient with nodular diabetic glomerulosclerosis.

We report a case of probable light- and heavy-chain deposition disease (LHCDD) in a diabetic patient, a rare and educational case. The patient was a 71-year-old man having a long history of uncontrolled diabetes mellitus with retinopathy. He showed heavy proteinuria and renal insufficiency, and did not have paraproteins. Renal biopsy revealed nodular glomerulosclerosis with severe mesangial widening and microaneurysm. Immunofluorescence (IF) showed weak staining of kappa light chain, IgG and C1q along glomerular basement membrane (GBM). At first, we interpreted these IF findings to be nonspecific, thus we diagnosed as diabetic nodular glomerulosclerosis. Later, we recognized one of a few case reports of monoclonal immunoglobulin deposition disease (MIDD) in diabetic patients, and reconsidered the first diagnosis. The added electron microscopy (EM) showed obvious electron-dense materials in GBM, while tubular basement membrane deposits were not identified. A concurrence of LHCDD and diabetic nodular glomerulosclerosis may be suggested in this case. Like this case, IF staining in MIDD is often weak, so it is difficult to diagnose MIDD accurately without EM. Reports of MIDD in diabetic patients are extremely rare, possibly due to being often overlooked. This case emphasizes that overall pathological examination including IF and EM is important for the accurate differentiation of nodular glomerulosclerosis, even in diabetic patients.

Diabetes influences peritoneal morphology in uremic patients at the initiation of peritoneal dialysis.

BACKGROUND: The peritoneum begins to undergo morphologic changes before the start of peritoneal dialysis (PD), particularly in diabetic patients. The present study was conducted to investigate the effects of diabetes on the peritoneum. METHODS: This study involved 17 patients who began receiving PD and had diabetes as an underlying disease (DM group), and 30 patients without diabetes who served as a control group (nonDM group). At the start of PD, the parietal peritoneum was sampled to assess submesothelial connective tissue thickness, number of capillaries and postcapillary venules, and indications of vasculopathy (grades 0 - 3). RESULTS: Submesothelial connective tissue thickness was significantly greater in the DM group than in the nonDM group (p < 0.01). The number of capillaries was significantly greater in the DM group (p < 0.01). Based on multivariate linear regression analysis, diabetes was identified as a significant independent variable of both submesothelial connective tissue thickness and number of capillaries (p < 0.01). CONCLUSIONS: In diabetic patients, morphologic changes of the peritoneum are marked at the start of PD.

Pseudorenal failure due to intraperitoneal bladder rupture after blunt trauma: usefulness of examining ascitic fluid sediment.

A 42-year-old man noted decreased urine output and visited our emergency department. He said that 3 days previously, he had gotten drunk and fallen down a set of stairs. Blood tests and abdominal contrast-enhanced computed tomography revealed no abnormalities. A serum creatinine level of 5.89 mg/dL led to a diagnosis of acute renal failure and his hospitalization. After admission, his ascitic fluid level gradually increased, suggesting urine leakage into the peritoneal cavity. Microscopic examination of his ascitic fluid sediment revealed the presence of hyaline casts enclosing renal tubular epithelial cells. Cystography demonstrated contrast medium leakage into the peritoneal cavity, which led to a diagnosis of bladder rupture. Examination of ascitic fluid sediment is simple and very useful for diagnosing bladder rupture.