Comparative outcomes of hemodialysis patients facing pre-Omicron and Omicron COVID-19 epidemics.

INTRODUCTION: This study elucidates factors affecting the severity and mortality in pre-Omicron and Omicron strains of SARS-CoV-2 and vaccination impact. METHODS: This single-center retrospective observational study included 1598 hospitalized COVID-19 patients. Patients were grouped into "pre-Omicron" and "Omicron" periods. The endpoint was severe COVID-19 (oxygen saturation [SpO2 ] < 94%). Logistic regression examined associations between clinical factors, including hemodialysis (HD), and the endpoint. RESULTS: The HD patient mortality rate dropped from 16% pre-Omicron to 4% during the Omicron epidemic. HD was significantly associated with the study endpoint in both epidemics. Unvaccinated patients had a greater risk of reaching the study endpoint among patients receiving HD. CONCLUSION: These findings suggest that the Omicron variant, alongside vaccination and healthcare innovations, led to improved prognoses for HD patients with COVID-19. However, HD patients remain at a greater risk for severe COVID-19. Increased vaccination rates and optimized healthcare resources can improve this vulnerable population's prognoses.

Serum chemokine CC-motif ligand 17 is a predictive marker of severe COVID-19 in haemodialysis patients: A retrospective observational study.

BACKGROUND: Maintenance haemodialysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID-19). Because of a limited number of facilities that can provide inpatient treatment for COVID-19 and HD, it is important to identify HD patients who are at high risk for severe COVID-19. For mild to moderate COVID-19 patients, chemokine CC-motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID-19; however, the validity of CCL17 among HD patients is unknown. METHODS: This retrospective observational study enrolled 107 HD patients with mild or moderate COVID-19 at hospitalization (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID-19. RESULTS: During hospitalization, 32 patients developed severe COVID-19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including lactate dehydrogenase and C-reactive protein for the prediction of severe COVID-19. The optimal cut-off value for CCL17 was 150.5 pg/mL. A multi-variate logistic analysis revealed that CCL17 (above 150.5 pg/mL) was significantly associated with severe COVID-19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017-0.227; p < .001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C-reacting protein and lactate dehydrogenase significantly improved classification performance for severe COVID-19 using the net reclassification (1.16, 95% CI: 0.82-1.50, p < .001) and integrated discrimination (0.18, 95% CI: 0.09-0.26, p < .001) improvement. CONCLUSION: CCL17 levels in HD patients with mild or moderate COVID-19 predict risk of developing severe COVID-19.

Reduced antibody response to SARS-CoV-2 in COVID-19 patients with newly diagnosed diabetes: a retrospective observational study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has dramatically impacted global health, and patients with type 2 diabetes have been identified as a high-risk group for COVID-19 infection and the development of severe disease. In response, this study aimed to evaluate whether patients with type 2 diabetes infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could develop antibody responses in the same manner as patients without diabetes, and whether there is a difference in antibody response to SARS-CoV-2 between patients with diabetes diagnosed prior to hospitalization, and those with newly diagnosed diabetes. METHODS: SARS-CoV-2-specific immunoglobulin G (IgG) levels were quantified using two iFlash 3000 Chemiluminescence Immunoassay analyzer kits (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for nucleocapsid protein (IgG-N), and specific for the S1 subunit of the spike protein (IgG-S1). In 124 hospitalized patients with COVID-19, 40 patients with type 2 diabetes were matched to 40 patients without diabetes using propensity score matching (PSM). RESULTS: There was no difference in IgG-N and IgG-S1 levels between the patients with diabetes and those without. Of patients with diabetes, 31 patients had known diabetes and nine patients had newly diagnosed diabetes. The median levels of IgG-N at 7-13 days in patients with newly diagnosed diabetes were significantly lower than those in patients with known diabetes (IgG-N; 10.9 vs. 31.0 AU/mL, p = 0.031, IgG-S1; 7.5 vs. 24.4 AU/mL, p = 0.023). CONCLUSIONS: Even after adjusting for covariates using PSM, COVID-19 patients with type 2 diabetes had comparable antibody responses to patients without diabetes. Patients with newly diagnosed diabetes had lower IgG-N and IgG-S1 production in the second week of the disease compared with those with previously known diabetes.

Efficacy and limitations of additional steroid pulse therapy in IgA nephropathy patients whose hematuria did not remit on tonsillectomy and protocol steroid pulse therapy.

BACKGROUND: Hematuria is the essential symptom of IgA nephropathy that has been suggested to be associated with long-term renal prognosis, Tonsillectomy and steroid pulse therapy (TSP), which is widely practiced in Japan, is effective for achieving hematuria remission. However, some cases are refractory to TSP, and additional steroid pulse therapy (SP) administered to these cases to achieve remission of hematuria. Nonetheless, the clinical significance of additional SP is unknown. METHODS: In this retrospective study, we enrolled 99 patients from Okubo Hospital whose hematuria persisted following TSP. Patients were divided into the hematuria remission and non-remission groups. A multivariate regression analysis was performed on the factors that contributed to hematuria remission. RESULTS: Following TSP, 103 of 403 patients (32.3%) did not achieve hematuria remission. Additional SP were performed in 99 of these patients, and remission of hematuria was achieved in 57 (57.6%). Patients with a greater degree of improvement in hematuria with TSP were significantly more likely to have remission of hematuria with additional SP (p = 0.0084*). Even in the hematuria non-remission group, both hematuria and proteinuria improved after additional SP. CONCLUSION: In IgA nephropathy, additional SP could induce hematuria remission and reduce proteinuria.

A case of COVID-19 reinfection in a hemodialysis patient: the role of antibody in SARS-CoV-2 infection.

Hemodialysis patients are vulnerable to severe and lethal COVID-19, and their protective immunity against COVID-19 is not yet fully understood. Therefore, we report a case of COVID-19 reinfection in a hemodialysis patient 81 days after the first episode and discuss the role of antibodies in SARS-CoV-2 infection. A hemodialysis patient developed asymptomatic COVID-19 due to an outbreak in a hospital on October 29th, 2020. As he was hospitalized and did not develop any symptoms, he was discharged on November 9th. On January 18th, he presented with symptomatic COVID-19 due to close household contact. Then, he developed respiratory failure and was transferred to National Center for Global Health and Medicine if he would need intensive care. He recovered with oxygen inhalation, favipiravir, and steroid treatment, and was discharged on February 12th. To evaluate anti-SARS-CoV-2 antibodies during two hospital stays, we measured immunoglobulin (Ig) G specific for S1 subunit of Spike (S) protein of SARS-CoV-2 (IgG-S1) , IgG specific for the full-length S protein (anti-Spike IgG) and neutralizing antibodies. No seroconversion occurred 5 days after initial infection, the seroconversion of IgG-S1 was observed 10 days after the second infection. Similar to IgG-S1 antibody titer results, anti-Spike IgG and neutralizing antibodies increased from 12 days after the second infection. In conclusion, we experienced a case of COVID-19 reinfection in a hemodialysis patient 81 days after the first episode and showed the kinetics and role of antibodies in SARS-CoV-2 infection. Further studies are needed to understand SARS-CoV-2 reinfection risk in hemodialysis patients and its clinical significance.

Hemodialysis patients with coronavirus disease 2019: reduced antibody response.

BACKGROUND: Because patients on maintenance hemodialysis (HD) have an impaired immune response to pathogens, they are at higher risk of severe coronavirus disease 2019 (COVID-19). However, data on antibody production among HD patients with COVID-19 is scarce. Thus, we performed a retrospective cohort study evaluating severe acute respiratory syndrome coronavirus two antibody (SARS-CoV-2) production within 1 month after COVID-19 onset in hospitalized patients on HD. METHODS: SARS-CoV-2-specific immunoglobulin (Ig) G levels were quantified using an iFlash 3000 Chemiluminescence Immunoassay analyzer (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for the S1 subunit of the spike protein (IgG-S1). Propensity score matching was used to balance covariate distribution in HD and non-HD patients. From April 2020 to February 2021, antibody testing was performed on 161 hospitalized patients with symptomatic COVID-19. Of them, 34 HD patients were matched to 68 non-HD patients. RESULTS: After propensity score matching, the median levels of IgG-S1 in the HD patients at 7-13 days after symptom onset were significantly lower than in non-HD patients, especially in those with severe disease. Among all patients, those with severe disease produced lower levels of IgG-S1 at 7-13 days compared with non-severe patients. CONCLUSION: COVID-19 patients with severe disease, especially those undergoing HD, had lower IgG-S1 production in the second week of the disease. Thus, the increased risk of severe COVID-19 in HD patients may be, in part, due to a slow and reduced antibody response.

Changes in Quality of Life in Older Hemodialysis Patients: A Cohort Study on Dialysis Outcomes and Practice Patterns.

BACKGROUND: Despite improvements in dialysis treatment, mortality rates remain high, especially among older hemodialysis patients. Quality of life (QOL) among hemodialysis patients is strongly associated with higher risk of death. This study aimed to describe the health-related QOL and its change in older maintenance hemodialysis patients and to demonstrate characteristics associated with health-related QOL. METHODS: Data on 892 maintenance hemodialysis patients aged 60 years or older who were surveyed using the Kidney Disease Quality of Life Short Form at baseline and 2 years after study enrollment in phases 4 (2009-2011) and 5 (2012-2014) of the Japanese Dialysis Outcomes and Practice Patterns Study were analyzed. We categorized participants into 3 age groups (60-69, 70-79, and ≥80 years) and described baseline physical component summary (PCS) and mental component summary (MCS) scores, as well as their distribution of changes after 2 years across each category. RESULTS: Hemodialysis patients aged 70-79 years and ≥80 years had lower PCS scores than those aged 60-69 years (median: 70-79 years = 43.1; interquartile range [IQR], 35.2-49.4; ≥80 years = 38.8; IQR, 31.6-43.8; 60-69 years = 45.4; IQR, 37.5-51.4; p < 0.001). In contrast, MCS scores did not significantly differ by age category (70-79 years = 45.6; IQR, 38.4-53.7; ≥80 years = 45.4; IQR, 36.9-55.1; 60-69 years = 46.8; IQR, 39.5-55.7; p = 0.1). As dialysis vintage lengthened, the PCS score significantly became lower, whereas no association was found with change in the MCS score. The MCS score declined over time in older patients, especially among those aged 80 years and older after 2 years' follow-up. CONCLUSIONS: Physical QOL became worse as dialysis vintage lengthened. In contrast, mental QOL declined over time within a relatively short period among older maintenance hemodialysis patients.

The Normalized Protein Catabolic Rate and Mortality Risk of Patients on Hemodialysis by Frailty Status: The Japanese Dialysis Outcomes and Practice Pattern Study.

OBJECTIVE: The appropriate protein intake for patients on hemodialysis complicated with frailty remains highly controversial. METHODS: We conducted a prospective cohort study using data from Japanese Dialysis Outcomes and Practice Pattern Study. The patients were separated by their baseline of normalized protein catabolic rate (nPCR) into 3 categories: low (nPCR < 1.0), medium (1.0 ≤ nPCR <1.2), and high (nPCR ≥1.2). The frailty score was calculated based on the 12-item Short Form, and frailty was defined in cases with a total score of ≥2 points. The all-cause mortality was compared between groups using a Cox proportional hazard model. RESULTS: A total of 2,404 patients were included in the longitudinal analysis, 1,096 (45.6%) of whom had frailty. Patients in the low-nPCR group showed a higher prevalence of frailty than those in the other groups. In the Cox proportional hazard model, no significant differences in the all-cause mortality were noted between the low-nPCR and medium-nPCR groups or the high-nPCR and medium-nPCR groups. Furthermore, no significant differences were noted among any groups when subjects were limited to patients with frailty. CONCLUSIONS: Patients with a low nPCR have a higher prevalence of frailty and incidence of mortality than those with a medium nPCR. Patients with a high nPCR did not show a lower survival rate than those with a medium nPCR in this study. To clarify the appropriate protein intake for patients on hemodialysis with frailty, an intervention study or large-scale, long-term cohort study will be needed.

A high titer of acquired factor V inhibitor in a hemodialysis patient who developed arterial thrombosis.

An 87-year-old man with diabetes mellitus was admitted to control recurrent bleeding from hemodialysis puncture sites. He was a smoker and had been diagnosed with arteriosclerosis obliterans. His PT and APTT were markedly prolonged, and all coagulation factors were markedly decreased (factor V [FV] activity < 1%) or below the measurement threshold, with the exception of fibrinogen and factor XIII. Neither PT nor APTT were corrected upon mixing with normal plasma. A high titer of FV inhibitor was found at 415 BU/mL, and anti-FV autoantibody was detected by both immunoblot assay and ELISA. Prednisolone administration and plasma exchange partially improved prolonged PT and APTT and decreased the FV inhibitor level. Five months later, he manifested symptoms of severe ischemia in both legs. Angiography revealed diffuse stenosis downstream of both common iliac arteries. Endovascular therapy was repeated four times, the prednisolone dose was reduced, and low-dose antiplatelet therapy was initiated. After the final successful endovascular therapy, arterial thrombosis was detected using ultrasound and angiography. Aspiration thrombectomy and thrombolytic therapy failed to achieve recanalization, and necrosis of the legs worsened. Despite the severe coagulation abnormalities, vascular interventions should have been performed with regular-dose antiplatelet therapy, as the patient exhibited multiple risk factors for atherothrombosis.

Ruptured renal artery in microscopic polyangiitis: a case report and literature review.

Medium-vessel hemorrhage is a rare occurrence in ANCA-associated vasculitis, and has been previously described in only a few patients with microscopic polyangiitis. We report a case of renal hemorrhage in a patient with microscopic polyangiitis that was successfully managed by transcatheter arterial embolization of the active bleeding sites. The early clinical findings included necrotizing arteritis, as indicated by skin biopsy; rapidly progressive glomerulonephritis; mononeuritis multiplex; positive screening for myeloperoxidase-specific antineutrophil cytoplasmic antibody. Corticosteroid therapy was initiated. The patient's health deteriorated at 1 week, with rapidly progressing anemia. Computerized tomography identified a large, right-sided, perirenal hematoma, with active bleeding. Bleeding was successfully managed via segmental embolization of the renal artery. The patient was treated with steroid therapy and MZR, and subsequently underwent maintenance hemodialysis treatment for end-stage renal disease. Spontaneous renal hemorrhage is a rare but fatal clinical condition. A ruptured renal artery should be considered in a patient with microscopic polyangiitis, even in the absence of previous trauma and renal biopsy, when unexplained anemia or signs of shock occur.

An Autopsy Case of Myeloperoxidase-anti-neutrophil Cytoplasmic Antibody (MPO-ANCA)-associated Vasculitis Accompanied by Cryoglobulinemic Vasculitis Affecting the Kidneys, Skin, and Gastrointestinal Tract.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and cryoglobulinemic vasculitis (CV) rarely coexist. An 83-year-old woman was admitted with rapidly progressive renal failure, gastrointestinal hemorrhage and purpura with myeloperoxidase (MPO)-ANCA positivity and cryoglobulinemia. Despite intensive immunosuppressive treatment, she died of aspergillus pneumonia. Autopsy revealed necrotizing crescentic glomerulitis in the majority of the glomeruli, accompanied by partially membranoproliferative-like glomerular changes. Immunofluorescence staining revealed the presence of neutrophil extracellular trap (NET) formation in the glomeruli and cutaneous arteries. These pathological findings suggested that MPO-AAV and/or CV caused NET formation, leading to lethal systemic vasculitis.

Clinical and Pathological Features of Plasma Cell-Rich Acute Rejection After Kidney Transplantation.

BACKGROUND: Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection characterized by the presence of mature plasma cells. In general, the prognosis of PCAR is poor, and its clinical and pathological features remain unclear. METHODS: We performed a retrospective observational study and compared allograft survival between kidney transplant recipients who developed PCAR and those who did not develop PCAR. We further analyzed clinical and pathological risk factors for allograft failure in PCAR patients. RESULTS: Of 1956 recipients, 40 developed PCAR. There was a higher prevalence of deceased donor transplants (27.5% vs 11.7%, P = 0.0059), longer median total ischemia time (99 minutes; interquartile range, 71-144 vs 77 minutes; interquartile range, 59-111; P = 0.0309), and lower prevalence of ABO-incompatible transplantation (7.5% vs 22.5%; P = 0.0206) in patients with PCAR than in those without PCAR.Multivariate Cox regression analysis showed that development of PCAR was associated with allograft loss (hazard ratio, 8.03; 95% confidence interval, 3.89-14.80; P < 0.0001).We classified PCAR according to the Banff 2015 criteria into a borderline change group, a T cell-mediated rejection (TCMR) group, an antibody-mediated rejection (AMR) or suspected of having AMR (AMR/sAMR) group, and a mixed rejection (TCMR/AMR) group. The AMR/sAMR group was associated with a lower rate of allograft survival without significant difference (log-rank test, P = 0.1692). CONCLUSIONS: The results indicated that PCAR was an independent risk factor for allograft loss. PCAR presented with all types of rejection in the Banff 2015 criteria, and AMR/sAMR was associated with poor allograft survival.

False Elevation of the Blood Tacrolimus Concentration, as Assessed by an Affinity Column-mediated Immunoassay (ACMIA), Led to Acute T Cell-mediated Rejection after Kidney Transplantation.

Tacrolimus is the most commonly used immunosuppressant. Because of its narrow therapeutic range, it is necessary to frequently monitor its concentration. We report the case of a 25-year-old man who underwent kidney transplantation whose tacrolimus concentrations, as measured by an affinity column-mediated immunoassay, were falsely elevated. As we reduced the dose of tacrolimus, the recipient developed T cell-mediated rejection. Using the same blood samples, an enzyme-multiplied immunoassay technique showed that the patient's levels of tacrolimus were extremely low. A further examination indicated that the false increase in the tacrolimus concentration was likely due to an unknown interfering substance. We administered methylprednisolone and antithymocyte-globulin. The patient's serum creatinine level decreased and remained stable after these treatments.

Preemptive anti-cytomegalovirus therapy in high-risk (donor-positive, recipient-negative cytomegalovirus serostatus) kidney transplant recipients.

OBJECTIVES: Universal prophylaxis and preemptive therapy are used to prevent cytomegalovirus (CMV) disease post-transplantation. Data regarding which strategy is superior are sparse, especially in high-risk recipients (donor CMV seropositive (D+) and recipient CMV seronegative (R-)). METHODS: This retrospective, single-center cohort study included recipients who underwent kidney transplantation between 2009 and 2015. The incidence of CMV infection/disease and patient and graft outcomes were analyzed and compared between high-risk recipients (D+/R-) and intermediate-risk recipients (D+/R+ or D-/R+), all managed with preemptive therapy. RESULTS: Of 118 kidney transplant recipients, 21 were high-risk and 97 were intermediate-risk. Over a median follow-up period of 3 years, asymptomatic CMV infection developed significantly more frequently in high-risk patients than in intermediate-risk patients (38.1% vs. 16.5%, p=0.04), and CMV disease developed in a similar manner (28.6% vs. 3.1%, p<0.01). Among high-risk patients, CMV infection developed within the first 3 months post-transplantation and CMV disease within the first 9 months post-transplantation. Kaplan-Meier analysis showed no difference in the probability of mortality (log-rank p=0.63) or graft loss (log-rank p=0.50) between the patient groups. Graft rejection occurred more frequently in high-risk than in intermediate-risk patients, but the difference was not significant (log-rank p=0.24). CONCLUSIONS: These results suggest that further studies on universal prophylaxis in high-risk patients are needed to elucidate whether preventing CMV infection/disease during the early post-transplant period leads to better outcomes, especially in terms of reducing graft rejection.

Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA Nephropathy.

The TNF family member a proliferation-inducing ligand (APRIL; also known as TNFSF13), produced by myeloid cells, participates in the generation and survival of antibody-producing plasma cells. We studied the potential role of APRIL in the pathogenesis of IgA nephropathy (IgAN). We found that a significant proportion of germinal centers (GCs) in tonsils of patients with IgAN contained cells aberrantly producing APRIL, contributing to an overall upregulation of tonsillar APRIL expression compared with that in tonsils of control patients with tonsillitis. In IgAN GC, antigen-experienced IgD-CD38+/-CD19+ B cells expressing a switched IgG/IgA B cell receptor produced APRIL. Notably, these GC B cells expressed mRNA encoding the common cleavable APRIL-α but also, the less frequent APRIL-δ/ζ mRNA, which encodes a protein that lacks a furin cleavage site and is, thus, the uncleavable membrane-bound form. Significant correlation between TLR9 and APRIL expression levels existed in tonsils from patients with IgAN. In vitro, repeated TLR9 stimulation induced APRIL expression in tonsillar B cells from control patients with tonsillitis. Clinically, aberrant APRIL expression in tonsillar GC correlated with greater proteinuria, and patients with IgAN and aberrant APRIL overexpression in tonsillar GC responded well to tonsillectomy, with parallel decreases in serum levels of galactose-deficient IgA1. Taken together, our data indicate that antibody disorders in IgAN associate with TLR9-induced aberrant expression of APRIL in tonsillar GC B cells.

Cardiovascular and Stroke Risk in Japanese Hemodialysis Patients With Atrial Fibrillation.

Atrial fibrillation is one of the most common arrhythmias in hemodialysis patients. We evaluated its clinical outcomes among hemodialysis patients with atrial fibrillation in Japan. Using data derived from the Japanese Dialysis Outcomes and Practice Patterns Study, we analyzed backgrounds and outcomes among hemodialysis patients with and without atrial fibrillation in Japan. Among 7002 hemodialysis patients, the prevalence of atrial fibrillation was 5.7% and the incidence was 0.2 per 100 patient-years. Atrial fibrillation was independently associated with all-cause mortality (hazard ratio, 1.32; 95% confidence interval, 1.02-1.71) and cardiovascular events (hazard ratio, 1.39; 95% confidence interval, 1.15-1.68), but not with stroke events (hazard ratio, 0.77; 95% confidence interval, 0.55-1.06) after adjustment for other variables. We conclude that patients with atrial fibrillation experienced higher mortality and more cardiovascular events than did patients without atrial fibrillation, although the risk of stroke was lower than expected.

Clinical and biochemical investigation of male patients exhibiting membranous cytoplasmic bodies in biopsied kidney tissues; a pitfall in diagnosis of Fabry disease.

BACKGROUND: The existence of membranous cytoplasmic bodies in biopsied kidney tissues is one of the important findings when considering Fabry disease as the first choice diagnosis. However, there are possible acquired lysosomal diseases associated with pharmacological toxicity, although less attention has been paid to them. CASE PRESENTATION: We experienced 3 male patients presenting with proteinuria and specific pathological changes strongly suggesting Fabry disease. We sought detailed clinical and biochemical information to avoid a wrong diagnosis. The patients were examined clinically and pathologically, and plasma α-galactosidase A (GLA) activity and the globotriaosylsphingosine (lyso-Gb3) concentrations were measured. Electron microscopic examination revealed numerous membranous inclusion bodies in podocytes, and biochemical analysis revealed normal GLA activity and a normal lyso-Gb3 level in plasma, showing that they did not have Fabry disease. They suffered from hyperlipidemia, myeloma, or lupus nephritis. They had received pitavastatin calcium, clarithromycin, loxoprofen and/or prednisolone, and there was no medication history of cationic amphiphilic drugs. CONCLUSIONS: In this case series, the etiology of the inclusions was not clarified. However, these cases indicate that careful attention should be paid on diagnosis of patients exhibiting inclusion bodies in kidney cells, and it is important to confirm their past and present illnesses, and medication history as well as to measure the GLA activity and lyso-Gb3 level.

Renal biopsy findings and clinical indicators of patients with hematuria without overt proteinuria.

BACKGROUND: Whether to perform a renal biopsy for isolated hematuria remains a matter of controversy. We performed renal biopsy in hematuria without overt proteinuria patients and reported the proportion of glomerulonephritis, pathological activities, and statistical analysis of indicators associated with glomerulonephritis. METHODS: Among 203 patients who underwent renal biopsy in Okubo Hospital, Japan, between January 2008 and October 2013, we identified 56 patients who fulfilled the criteria: (1) urine dipstick examination shows equal to or greater than ± blood on three or more visits, (2) proteinuria <0.3 g/day (g/g Cr), (3) eGFR ≧60 ml/min/1.73 m(2), and (4) no current medication for renal disease. We investigated biopsy findings and compared the clinical indicators in the IgA nephropathy (IgAN) and non-IgAN group. RESULTS: The pathological diagnosis was IgAN in 35 cases (62 %), thin basement membrane disease (TBMD) in 7 (13 %), minor glomerular abnormality (MGA) in 6 (11 %), glomerular basement membrane (GBM) abnormality in 5 (9 %), and others in 3 (5 %). The histological grade of IgAN was I in 90 % and II in 10; 31 % of patients had some crescentic lesions. Comparisons between the IgAN and non-IgAN group revealed significant differences in age of onset (26 ± 13 vs. 34 ± 17 years, p = 0.04), serum IgA (340 ± 114 vs. 220 ± 101 mg/dl, p < 0.01), proteinuria (0.08 [0-0.25] vs. 0 [0-0.23] g/day [g/gCr], p < 0.01), and the presence of poikilocytes (40 vs. 10 %, p = 0.02). CONCLUSIONS: The proportion of IgAN in hematuria without overt proteinuria was high and the pathological activities were variable. Patients with hematuria without overt proteinuria should continue their medical follow-up and the best timing of biopsy may be controversial for these patients who have multiple risk factors of IgAN.

Simultaneous nephrotic syndrome and hepatitis in secondary syphilis: case report and review of the literature.

A 66-year-old man presented with a penile ulcer, an acute clinical onset of nephrotic syndrome and hepatitis. Secondary syphilis was diagnosed on the basis of the history of rash and the result of strongly positive serological test for syphilis. A renal biopsy demonstrated membranous glomerulonephritis with subepithelial electron-dense deposits. After treatment with amoxicillin for 2 weeks, he achieved clinical recovery. It is important to recognize syphilis as a reversible cause of nephrotic syndrome and acute hepatitis because antibiotic therapy can result in complete remission.