Takuya Miki

Is there a link between diabetic glomerular injury and crescent formation? A case report and literature review

Glomerular crescents are most commonly associated with rapidly progressive crescentic glomerulonephritis; however, they also develop in response to a wide range of primary and secondary glomerular injuries. Since various kind of glomerulopathies occasionally overlay diabetic glomerular injuries, the presence of crescents in renal biopsy specimens of diabetics may have stimulated a search for etiologies other than diabetes. In this report, we describe an unusual case of diabetic glomerulosclerosis with peculiar extracapillary proliferation. Although such a relationship has so far been ignored in most of the literature, the etiological linkage between diabetic glomerulosclerosis and the development of crescents may not be exceptional. We have reviewed the previous literature and herein discuss the pathological implications of the development of crescents in patients with diabetic glomerulosclerosis.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3950457896920255.

Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients

Klotho is a single-pass transmembrane protein predominantly expressed in the kidney. The extracellular domain of Klotho is subject to ectodomain shedding and is released into the circulation as a soluble form. Soluble Klotho is also generated from alternative splicing of the Klotho gene. In mice, defects in Klotho expression lead to complex phenotypes resembling those observed in dialysis patients. However, the relationship between the level of serum soluble Klotho and overall survival in hemodialysis patients, who exhibit a state of Klotho deficiency, remains to be delineated. Here we prospectively followed a cohort of 63 patients with a mean duration of chronic hemodialysis of 6.7 ± 5.4 years for a median of 65 months. Serum soluble Klotho was detectable in all patients (median 371 pg/mL, interquartile range 309–449). Patients with serum soluble Klotho levels below the lower quartile (<309 pg/mL) had significantly higher cardiovascular and all-cause mortality rates. Furthermore, the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29–13.48). We conclude that there may be a threshold for the serum soluble Klotho level associated with a higher risk of mortality.

Membranous nephropathy in an HIV-positive patient complicated with hepatitis B virus infection

In ordinary settings, human immunodeficiency virus (HIV)-associated nephropathy should be considered when HIV infection is associated with heavy proteinuria. On the other hand, hepatitis B virus (HBV) may also play a role in the development of glomerular injury among patients with HIV infection, since HIV and HBV infections commonly occur together due to shared modes of transmission. We present here a case of nephrotic syndrome in an HIV-positive patient complicated with HBV infection. A renal biopsy revealed sparse granular deposits of immunoglobulin G in the subepithelial region, consistent with membranous nephropathy (MN) stage I. Moreover, immunostaining exhibited weak anti-hepatitis B core activity within glomeruli. These results led us to consider that HBV-associated MN might play a role in the development of nephrotic syndrome. Although anti-viral treatment for patients with HBV-associated MN has been suggested to be clinically effective, the use of two anti-HIV agents (tenofovir and emtricitabine), both of which have anti-HBV activities, was not effective for the patient’s nephrotic syndrome, despite obtaining a decrease in the serum HBV-DNA levels. A lack of prospective data suggests that many decisions on the treatment of glomerulopathies with HIV infections are potentially empirical. Obviously, further studies and accumulated clinical experience are required to better determine the pathogenesis and management of HBV-associated MN among patients with HIV infections.

Therapeutic Challenges to End-Stage Kidney Disease in a Patient with Tetralogy of Fallot

In this report, we describe the case of an end-stage kidney disease patient with tetralogy of Fallot (TOF). A 33-year-old female with TOF was admitted to our hospital with complaints of general fatigue and appetite loss probably due to uremic milieu. She was ultimately treated with peritoneal dialysis (PD) with a favorable clinical course. TOF patients with chronic kidney disease are not exceptional, although the currently available information regarding the association between TOF and renal failure severe enough to require dialysis treatment is limited. We also discuss the complex processes of how and why PD was selected as a mode of chronic renal replacement therapy in this case.

Tubulointerstitial Nephritis and Uveitis Syndrome: Are Drugs Offenders or Bystanders?

A 16-year-old female patient was admitted to our hospital due to progressive renal dysfunction with an increased serum creatinine (sCr) level of 1.7 mg/dL. Her clinical course without any ocular manifestations and results of drug-induced, lymphocyte-stimulating tests, in addition to a renal histological assessment, initially encouraged us to ascribe the patients renal abnormalities to drug-induced acute interstitial nephritis (AIN). Four months later, she started to complain about reduced visual acuity when she was found to have anterior bilateral uveitis despite the recovered renal function with almost constant sCr levels around 0.7 mg/dL. Thus, a diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was finally made. Our case illustrates the difficulties in distinguishing late-onset uveitis TINU syndrome from drug-induced AIN at the time of the renal biopsy, thereby suggesting the importance of a longitudinal follow-up to overcome the potential underdiagnosis of the disease. Several diagnostic conundrums that emerged in this case are also discussed.

Rituximab Treatment for PR3-ANCA-Positive Membranoproliferative Glomerulonephritis Associated with Adult-Onset Periodic Fever Syndrome

We report the case of a 36-year-old Japanese woman with nephrotic syndrome due to membranoproliferative glomerulonephritis (MPGN) Type I diagnosed after a 5-year history of periodic fever syndrome (PFS). Hypocomplementemia and elevation of anti-proteinase 3 anti-neutrophil cytoplasmic autoantibody (PR3-ANCA) were observed. HIV, and hepatitis B and C serology were negative. Nephrotic syndrome and periodic fever did not respond to oral steroid and intravenous steroid pulse therapies combined with cyclosporine, dipyridamole, warfarin and losartan. We tried immunotherapy using rituximab, a human-mouse chimeric monoclonal antibody directed against the CD20 antigen on mature B cells. This therapeutic approach led to improvement of renal function and remission of nephrotic syndrome and hypocomplementemia. However, it did not have a beneficial effect on periodic fever. Suspecting adult-onset hereditary PFS, we analyzed her genetic alteration of MEFV and TNFRSF1A genes. A rare genotype in intron 6 of TNFRSF1A was revealed. The etiological relationship between periodic fever and MPGN is discussed. Rituximab is a hopeful choice of induction therapy for refractory MPGN.

Acute Kidney Injury Associated with Renal Cell Carcinoma Complicated by Renal Vein and Inferior Vena Cava Involvement.

Acute kidney injury (AKI) is caused by diverse pathologies, although it may occasionally result from concurrent renal efflux disturbances. We herein describe a case of AKI in a patient complicated by renal cell carcinoma (RCC) with renal vein and inferior vena cava (IVC) involvement. A neoplastic thrombus which disrupted the blood flow in the renal vein appeared to play a role in the rapid decline in the renal function. Such a scenario has rarely been mentioned in the previous literature describing the cases of RCC complicated by AKI. Concerns regarding the diagnostic and therapeutic strategies for RCC are also discussed.

Development of Acute Pericarditis Associated with New-onset Rheumatoid Arthritis in a Diabetic Patient with Renal Impairment: The Elusive Nature of Uremia

Uremic patients may have a variety of organ involvement, however, the precise causality may be impossible to determine in some cases because the symptoms of uremia are also associated with other diseases. With an emphasis on the elusive nature of uremia, we herein describe a 53-year-old man with preexisting renal impairment who developed acute pericarditis with deterioration of his renal function. Hemodialysis was immediately initiated on the presumption of uremia, however, articular symptoms emerged approximately a month later and led to a final diagnosis of rheumatoid arthritis, followed by successful withdrawal of hemodialysis.

Prevalence of colorectal carcinoma in CKD patients in pre-dialysis and during the dialysis introduction period

To the Editor Chronic kidney disease (CKD) is a risk factor for malignant disease (MD), but the relationship between these aliments remains to be elucidated. Recently, Wu et al. [1] reported on the increased colorectal cancer (CRC) incidence in Taiwanese CKD patients. In Japan, there are few epidemiological data on non-dialysis CKD patients with MD. Therefore, we conducted a single-center retrospective survey to explore the previous history and the prevalence of MD in CKD patients, treated at Jichi Medical School Hospital between January 2008 and December 2013, using the dialysis-introduction database. The study was performed in accordance with the Declaration of Helsinki and was approved by the Ethical Committee of Jichi Medical University (epidemiology 13–95). The dialysis introduction period (DIP) was determined as being within 1 year before and after dialysis administration. Acute kidney injury cases that had quit dialysis within 2 months of its initiation were excluded. Out of 724 dialysis introduction patients [464 were male; age of dialysis introduction: 64 (mean) ± 14 (SD)], 44 cases had a previous history of MD, 55 cases had newly diagnosed MD during the DIP (Table 1) and five cases had both previously and newly diagnosed MD. Within previously-diagnosed and newly-diagnosed MD cases, CRC ranked first in both. During the DIP, CRC tended to be diagnosed in the early stage. Furthermore, most of the CRCs were adenocarcinomas and one was a neuroendocrine carcinoma. Serum creatinine level and amount of urine protein at the time of diagnosis of predialysis CRC were 1.70 ± 0.57 mg/dL and 3.3 ± 2.8 g/g creatinine, respectively. Among pre-dialysis and DIP CRC patients, none had received adjuvant chemotherapy and only one patient had taken oral alfacalcidol prior to being diagnosed with CRC. Considering that CRC has been found to be third in terms of incidence of MD in the general Japanese male population and that the crude rate of CRC in the same population was 105.5/10 [2, 5], the prevalence of CRC in this CKD population appears to be relatively high. Four causal associations between CKD and CRC were assumed to have occurred. One was a hypovitaminosis D and another was an abnormality of folate and homocysteine metabolism [3]. CKD has been shown to be a well-known cause of hypovitaminosis [4], and hypovitaminosis D has been found to be a principal epidemiological factor of CRC [5]. However, the significance of hypovitaminosis D and vitamin D receptor polymorphisms in CRC in CKD patients has not been investigated. Treatment-related kidney injuries including chemotherapy-induced acute tubular necrosis and cancer-associated nephropathy are also suggested causes. To understand more the relationship between CRC and CKD will likely require a multicenter C. Ito (&) T. Akimoto T. Miki E. Kusano D. Nagata Division of Nephrology, Department of Medicine, School of Medicine, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan e-mail: ichiharu@jichi.ac.jp