Renal tubular necrosis associated with anagrelide administration: a case report.

A 62-year-old female patient with essential thrombocythemia experienced rapid renal dysfunction and was subsequently referred to our hospital. Further investigations did not reveal any significant abnormalities except for a slight increase in urinary ß2-microglobulin levels. A renal biopsy was performed to investigate the cause of her renal dysfunction, revealing acute tubular necrosis, interstitial edema, and arteriosclerosis. No significant glomerular lesions were observed. Immunofluorescence staining and electron microscopy showed no abnormalities. She had been using anagrelide for 4 years, and her dosage was increased from 2.0 to 3.0 mg/day 10 months before her initial admission. Her renal function began to deteriorate 2 months after the anagrelide dosage increase. Although 0.625 mg of bisoprolol was initiated for tachycardia 3 months after the anagrelide dosage adjustment, we suspected that the acute tubular necrosis was associated with anagrelide administration. After transitioning from anagrelide to hydroxyurea and discontinuing bisoprolol, her renal function improved. This case suggests the importance of considering anagrelide as a potential cause of renal dysfunction in patients using this medication. Therefore, renal biopsy, combined with a comprehensive medical history, is crucial for evaluating the etiology of renal injury in such cases.

Improvement of Light Chain Proximal Tubulopathy without Crystals in IgGλ-type Monoclonal Gammopathy of Undetermined Significance Using Bortezomib and Dexamethasone.

A 70-year-old woman with acute kidney injury, a high serum Creatinine (Cr) level (3.91 mg/dL), and proteinuria (protein/Cr ratio 1.59 g/gCr) was admitted. Serum IgG λ-type and urinary λ-type M proteins were observed. A bone marrow examination indicated monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy showed distended proximal tubular cells, and immunofluorescence identified tissue positive for proximal tubular cell λ light chains. Electron microscopy identified fibril-like structures in the lysosomes. The patient was diagnosed with light chain proximal tubulopathy without crystals in IgG λ-type MGUS and treated with bortezomib and dexamethasone therapy, which improved her renal function.

Immunoglobulin G deposition on proximal tubules and the tubular basement membrane in acute tubular injury complicated with focal segmental glomerulosclerosis (FSGS): A possible prediction tool for subclinical FSGS.

Immunofluorescent deposition of immunoglobulin G (IgG) in the tubular basement membrane (TBM) has been evaluated in the diagnosis of various diseases; however, few studies have investigated the immunofluorescence of acute tubular injury (ATI). Herein, we attempted to clarify IgG expression in the proximal tubular epithelium and TBM in ATI due to various causes. Patients with ATI with nephrotic-range proteinuria, including focal segmental glomerulosclerosis (FSGS, n = 18) and minimal change nephrotic syndrome (MCNS, n = 8), ATI with ischemia (n = 6), and drug-induced ATI (n = 7), were enrolled. ATI was evaluated by light microscopy. CD15 and IgG double staining and IgG subclass staining were performed to evaluate immunoglobulin deposition in the proximal tubular epithelium and TBM. IgG deposition was identified in the proximal tubules only in the FSGS group. Furthermore, IgG deposition in the TBM was observed in the FSGS group showing severe ATI. IgG3 was predominantly deposited by the IgG subclass study. Our results indicate that IgG deposition in the proximal tubular epithelium and TBM suggests the leaking of IgG from the glomerular filtration barrier and its reabsorption by proximal tubules, which may predict disruption of the glomerular size barrier, including subclinical FSGS. FSGS with ATI should be included as a differential diagnosis when IgG deposition in TBM is observed.

An Autopsy Case of An Acute Exacerbation of Idiopathic Pulmonary Fibrosis Triggered by the Inhalation of a Waterproofing Spray.

An 82-year-old Japanese man with idiopathic pulmonary fibrosis (IPF) experienced dyspnea after using a waterproofing spray in a closed room. He presented with hypoxemia and his chest computed tomography showed additive bilateral diffuse ground-glass attenuation on fibrosis, which was diagnostic of an acute exacerbation of IPF (AE-IPF). Combined treatment with high-dose corticosteroids and immunosuppressants were ineffective, and he later died of respiratory failure. Autopsy findings showed diffuse alveolar damage with honeycombing. His medical history and autopsy histopathology suggested AE-IPF caused by the inhalation of a waterproofing spray.

Correlation between renal distribution of leptospires during the acute phase and chronic renal dysfunction in a hamster model of infection with Leptospira interrogans.

BACKGROUND: Leptospirosis has been described as a biphasic disease consisting of hematogenous dissemination to major organs in the acute phase and asymptomatic renal colonization in the chronic phase. Several observational studies have suggested an association between leptospirosis and chronic kidney disease (CKD). We investigated the dynamics of leptospires and histopathological changes in the kidney to understand the relationship between them, and also investigated the extent of renal dysfunction in the acute and chronic phases of leptospirosis using a hamster model. FINDINGS: Hamsters (n = 68) were subcutaneously infected with 1 × 104 cells of the Leptospira interrogans serovar Manilae strain UP-MMC-SM. A total of 53 infected hamsters developed fatal acute leptospirosis, and the remaining 15 hamsters recovered from the acute phase, 13 of which showed Leptospira colonization in the kidneys in the chronic phase. Five asymptomatic hamsters also had renal colonization in the chronic phase. Immunofluorescence staining showed that leptospires were locally distributed in the renal interstitium in the early acute phase and then spread continuously into the surrounding interstitium. The kidneys of the surviving hamsters in the chronic phase showed patchy lesions of atrophic tubules, a finding of chronic tubulointerstitial nephritis, which were substantially consistent with the distribution of leptospires in the renal interstitium. The degree of atrophic tubules in kidney sections correlated statistically with the serum creatinine level in the chronic phase (rs = 0.78, p = 0.01). CONCLUSION: Subcutaneous infection with pathogenic leptospires could cause acute death or chronic leptospirosis in hamsters after surviving the acute phase. We suggest that the renal distribution of leptospires during the acute phase probably affected the extent of tubular atrophy, leading to CKD.

Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3-5 chronic kidney disease: a prospective observational study.

BACKGROUND: Blood urea nitrogen (BUN) is one of the substances that affects the calculated serum osmolality (cSosm). A previous study demonstrated that BUN and cSosm were independently associated with the development of chronic kidney disease (CKD) in patients with preserved kidney function. In advanced CKD stages, there is a concomitant increase in cSosm and BUN levels. However, it remains unclear whether BUN or cSosm levels are related to renal outcomes in patients with moderate to severe kidney dysfunction. The aim of this study was to clarify whether the BUN or cSosm level is associated with kidney disease progression in patients with advanced CKD. METHODS: In this prospective study, we enrolled 459 patients with CKD (stages 3-5). The composite renal endpoint was end-stage renal disease (ESRD) or death, and ESRD alone was added as an alternative outcome. A Cox proportional hazards model was utilized to determine the risk factors for a poor renal outcome. We adjusted for covariates including estimated glomerular filtration rate (eGFR). The cSosm (mOsm/kg) was calculated using the following formula: (2 × sodium) + (BUN/2.8) + (glucose/18). RESULTS: During a median follow-up of 25.8 months, the renal endpoint was observed in 210 patients. Multivariable Cox analysis determined the hazard ratio (HR) [95% confidence interval (CI)] for the composite renal outcome in the second, third, and fourth BUN quartiles were 1.36 (0.72-2.58), 1.87 (0.95-3.66), and 2.66 (1.23-5.76) (P for trend < 0.01), respectively compared with the first BUN quartile. Conversely, by multivariable Cox analysis, the HRs (95% CIs) for poor outcomes in the second, third, and fourth cSosm quartiles, compared with the first cSosm quartile, were 1.13 (0.69-1.87), 0.95 (0.58-1.55), and 1.26 (0.78-2.03), respectively (P for trend = 0.39). In addition, with regard to the renal outcome of ESRD alone, higher BUN quartiles had a significantly increased risk for the outcome, but cSosm levels were not associated with the outcome. CONCLUSIONS: Higher BUN levels, but not cSosm levels, were associated with adverse renal outcomes independent of the eGFR, suggesting that BUN may be a useful marker for predicting kidney disease progression.

High neutrophil/lymphocyte ratio is associated with poor renal outcomes in Japanese patients with chronic kidney disease.

BACKGROUND: Several studies have shown that the neutrophil/lymphocyte ratio (NLR) is a marker that reflects the state of systemic inflammation. A high NLR was reported to be associated with cardiovascular events and mortality. However, little is known about the association between NLR and kidney disease progression in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to determine whether NLR is associated with renal outcomes in CKD patients. METHODS: This prospective observational study included 350 consecutive patients with stage 1-4 CKD treated between June 2009 and November 2016. Data were collected until June 2017. The endpoint was the composite of end-stage renal disease requiring dialysis or death. Subjects were divided into two groups according to high and low NLR levels. A Cox proportional hazards model was used to determine the risk factors for composite outcomes. RESULTS: The composite endpoint was observed in 83 patients during the median follow-up period of 31.8 months: 29 in the low NLR group and 54 in the high NLR group. Multivariable analysis showed that the high NLR group had a significant increase in the hazard ratio (HR) for composite outcomes (HR 1.67, 95% confidence interval 1.02-2.77) compared with the low NLR group. CONCLUSION: The present study demonstrated that a high NLR was associated with poor renal outcomes, suggesting that NLR may be a useful marker for prognostic prediction in patients with CKD.

Comparison of Prognostic Values of Daytime and Night-Time Systolic Blood Pressures on Renal Outcomes in Patients With Chronic Kidney Disease.

BACKGROUND: Differences in the predictive value of daytime systolic blood pressure (SBP) and night-time SBP by ambulatory blood pressure monitoring on renal outcomes have not been fully investigated in chronic kidney disease (CKD) patients. This study compared the prognostic value between daytime and night-time SBP on renal outcomes in CKD.Methods and Results:This prospective observational study included 421 patients. The composite renal endpoint was endstage renal disease (ESRD) or death. Cox models were used to determine associations of daytime and night-time SBP with renal outcomes. There were 150 renal events (ESRD, 130; death, 20). Multivariable Cox analyses demonstrated that hazard ratios (HRs) [95% confidence interval (CI)] for composite renal outcomes of every 10-mmHg increase in daytime and night-time SBP levels were 1.13 (1.02-1.26) (P=0.02) and 1.15 (1.05-1.27) (P<0.01), respectively. In addition, compared with the 1st daytime or night-time SBP quartile, HRs (95% CI) for outcomes in the 2nd, 3rd, and 4th quartiles were: daytime SBP, 1.25 (0.70-2.25), 1.09 (0.61-1.94), and 1.58 (0.88-2.85; P=0.13) (P for trend=0.16); night-time SBP, 1.09 (0.61-1.96), 1.31 (0.76-2.28), and 1.82 (1.00-3.30; P=0.049) (P for trend=0.03), respectively. CONCLUSIONS: Night-time SBP appeared superior to daytime SBP for predicting renal outcomes in this population of patients.

Associations of fibroblast growth factor 23 with urate metabolism in patients with chronic kidney disease.

OBJECTIVE: In patients with preserved kidney function, a positive association of fibroblast growth factor 23 (FGF23) with serum uric acid (SUA) has been reported; however, the relationship in overall chronic kidney disease (CKD) patients has not been investigated. No report has examined the relationship between FGF23 and uric acid clearance (CUA). The aim of the present study was to determine whether FGF23 is independently associated with urate metabolism in patients with CKD stages 1-5. MATERIALS AND METHODS: In this cross-sectional study, 537 CKD patients were enrolled. SUA, CUA, FGF23, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Multivariable linear regression analysis was applied to determine independent factors associated with SUA or CUA. RESULTS: In all patients, both SUA and CUA were independently associated with male sex, use of diuretics, use of uric acid-lowering agents, estimated glomerular filtration rate, and log FGF23 (ß=0.29, P<0.01 for SUA; ß=-0.11, P<0.01 for CUA), but not with log PTH or log 1,25(OH)2D. Dyslipidemia and diabetes were also independent factors for SUA and CUA, respectively. In multivariable analyses by sex, log FGF23 was associated with SUA in both sexes (ß=0.32, P<0.01 in males vs. ß=0.20, P=0.02 in females). Conversely, log FGF23 was independently associated with CUA in males (ß=-0.15, P<0.01), but not in females (ß=-0.09, P=0.17). CONCLUSIONS: FGF23 was independently associated with urate metabolism in this population of CKD patients. FGF23 might also have a stronger association with urate metabolism in males compared with females.

Long-Term Maintenance of Complete Response after Sorafenib Treatment for Multiple Lung Metastases from Hepatocellular Carcinoma.

Sorafenib is an effective treatment for unresectable hepatocellular carcinoma (HCC) characterized by disease stabilization. However, the response rates are very low (<9%percnt;), and a complete response is rarely achieved. We report an extremely rare case of a HCC patient with multiple lung metastases treated with sorafenib who achieved a complete response for a long period. A 77-year-old woman was diagnosed with chronic hepatitis C in 1990. In 2007, a HCC detected in the liver was treated with percutaneous ethanol injection therapy. Subsequently, recurrence of HCC in the liver was treated with microwave coagulonecrotic therapy in 2010. In April 2011, a computed tomography (CT) scan revealed innumerable multiple metastases spread diffusely in both lungs. Tumor marker levels were extremely high [α-fetoprotein (AFP) 76,170 ng/ml, lens culinaris agglutinin-reactive fraction of AFP 7.5%percnt;, des-γ-carboxyprothrombin (DCP) 63,400 mAU/ml]. Sorafenib was administered at a reduced dose of 400 mg/day because of old age. Four months after sorafenib treatment, AFP and DCP had decreased to within normal levels, and the multiple lung metastases had disappeared. Currently, sorafenib is administered at a reduced dose of 400 mg/day, and the complete response has been maintained for 48 months.