Effects of salt intake reduction by urinary sodium to potassium ratio self-monitoring method.

Effective and feasible educational methods are needed to control salt intake. We performed a single-center, non-randomized controlled study to investigate the effectiveness and feasibility of self-monitoring using a urinary sodium/potassium (Na/K) ratio-measuring device in patients with difficulty in reducing salt intake. This study included 160 patients with hypertension, chronic kidney disease, or heart disease who were followed up in the outpatient clinic of the Dokkyo Medical University Nikko Medical Center. Urinary Na/K ratio measuring Na/K ratio meter were loaned for 2-6 weeks to the treatment (T) group (n = 80) and not to the patients in the control (C) group (n = 80). In the T group, patients were instructed to measure the urinary Na/K ratio at least three times a day and maintain a Na/K ratio below 2.0. Salt reduction education and home blood pressure measurement guidance continued in both groups. The mean device loan period in the T group was 25.1 days, the mean number of measurements was 3.0 times/day, and the proportion of patients achieving three measurements per day was 48.8% (39/80). Self-monitoring using the urinary Na/K ratio meter successfully reduced salt intake by -1.9 g/day at the second visit (p < 0.001) in the T group. In contrast, no change was observed over time in the C group. Self-monitoring using the urinary Na/K ratio meter successfully reduced salt intake in patients with difficulty reducing salt intake.

Five-year trends in bacterial contamination of dialysis equipment.

Bedside dialysis monitoring equipment for hemodialysis are located in the bioburden section upstream of the endotoxin-retentive filter for dialysis fluid sterilization. We observed 26 equipment at our institution for bacterial contamination at least once every 4 weeks for 5 years with another ultrafiltration membrane upstream to prevent bacterial contamination. Bacterial contamination levels were highest and most diverse at the time of the first flush. During subsequent initial cleanng, the contamination level decreased, and bacterial species converged almost exclusively to one genus, namely Methylobacterium spp. During clinical use, the equipment were cleaned and disinfected daily after dialysis, and daily operations and maintenance were performed using aseptic techniques. Although the frequency of bacterial detection decreased annually, the same bacterial genotypes observed at the first flush were isolated even after long time periods and were thought to persist in the equipment possibly by forming biofilm. Pseudomonas aeruginosa was newly detected after the replacement of parts during breakdown maintenance, indicating the need to sterilize replacement parts. Thus, the bioburden should be assessed regularly as part of the management of in-house-produced dialysis fluid.

Effect of Pemafibrate on Hemorheology in Patients with Hypertriglyceridemia and Aggravated Blood Fluidity Associated with Type 2 Diabetes or Metabolic Syndrome.

Persistent high serum triglyceride (TG) and free fatty acid (FFA) levels, which are common in metabolic syndrome and type 2 diabetes, are risk factors for cardiovascular events because of exacerbated hemorheology. To explore the effects of pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, on hemorheology, we performed a single-center, nonrandomized, controlled study in patients with type 2 diabetes (HbA1c 6-10%) or metabolic syndrome, with fasting TG levels of ≥ 150 mg/dL and a whole blood transit time of > 45 s on a microarray channel flow analyzer (MCFAN). Patients were divided into a study group, receiving 0.2 mg/day of pemafibrate (n = 50) for 16 weeks, and a non-pemafibrate control group (n = 46). Blood samples were drawn 8 and 16 weeks after entry to the study to evaluate whole blood transit time as a hemorheological parameter, leukocyte activity by MCFAN, and serum FFA levels. No serious adverse events were observed in either of the groups. After 16 weeks, the pemafibrate group showed a 38.6% reduction in triglycerides and a 50.7% reduction in remnant lipoproteins. Pemafibrate treatment did not significantly improve whole blood rheology or leukocyte activity in patients with type 2 diabetes mellitus or metabolic syndrome complicated by hypertriglyceridemia and exacerbated hemorheology.

Long-Term Tailor-Made Exercise Intervention Reduces the Risk of Developing Cardiovascular Diseases and All-Cause Mortality in Patients with Diabetic Kidney Disease.

This study aimed to determine the effect of long-term exercise on the risk of developing cardiovascular diseases (CVD) and all-cause mortality in patients with diabetic kidney disease (DKD). A single-center, prospective intervention study using propensity score matching was performed over 24 months. The intervention group (n = 67) received six months of individual exercise instruction from a physical therapist, who performed aerobic and muscle-strengthening exercises under unsupervised conditions. New events were defined as the composite endpoint of stroke or CVD requiring hospitalization, initiation of hemodialysis or peritoneal dialysis, or all-cause mortality. The cumulative survival rate without new events at 24 months was significantly higher in the intervention group (0.881, p = 0.016) than in the control group (n = 67, 0.715). Two-way analysis of variance revealed a significant effect of the group factor on high density lipoprotein-cholesterol (HDL-C) which was higher in the intervention group than in the control group (p = 0.004); eGFRcr showed a significant effect of the time factor, which was lower at 24 months than before intervention (p = 0.043). No interactions were observed for all items. In conclusion, aerobic exercises combined with upper and lower limb muscle strengthening for six months reduce the risk of developing CVD and all-cause mortality in patients with DKD.

Anti-MDA5 Antibody-positive Dermatomyositis with Rapidly Progressive Interstitial Pneumonia Presenting with Nephrotic Syndrome during Treatment with Corticosteroids and Cyclosporine.

A 50-year-old Japanese woman with anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 antibody)-positive dermatomyositis presenting with rapidly progressive interstitial pneumonia was treated with corticosteroids and cyclosporine. She developed nephrotic syndrome during the treatment regimen with corticosteroids and cyclosporine. A kidney biopsy revealed a thrombotic microangiopathy (TMA) glomerular lesion. Anti-MDA5 antibody-positive dermatomyositis is prone to severe interstitial lung disease (ILD) and is often exacerbated and refractory to treatment. Renal symptoms might be due to TMA of the kidney, and this may be a sign that more intensive treatment is needed. Patients sometimes develop acute kidney injury, which may be due to the TMA.

Decreased Physical and Daily Living Activities in Patients with Peripheral Arterial Disease on Hemodialysis.

Decreased physical activity and activities of daily living (ADL) in patients on hemodialysis (HD) are associated with a poor prognosis. Additionally, comorbid peripheral arterial disease is associated with further deterioration. We conducted a cross-sectional study of ADL difficulty and life-space assessment (LSA) in three groups of patients on hemodialysis according to their ankle-brachial index (ABI) values. The 164 patients were divided into ABI Low (ABI < 0.9), Normal (0.9 ≤ ABI < 1.3), and High (1.3 ≤ ABI) groups, and compared using analysis of covariance with LSA and ADL difficulty adjusted for age. The Kihon checklist (KCL) was used to assess the presence of frailty. The LSA was lower in the Low group than in the High group (F = 3.192, p = 0.044). Similarly, the ADL difficulty was significantly lower in the Low group than in the Normal group (F = 3.659, p = 0.028). In the Low group, the proportion of patients with frailty was 47.1% and KCL physical was significantly lower, indicating that patients on HD with a lower ABI had a higher prevalence of frailty and lower LSA and ADL difficulty. In conclusion, patients on HD with decreased ABI values most likely exhibit decline in physical activity and ADL due to frailty and claudication.

Genetic Background and Clinicopathologic Features of Adult-onset Nephronophthisis.

INTRODUCTION: Recently, nephronophthisis (NPH) has been considered a monogenic cause of end-stage renal disease (ESRD) in adults. However, adult-onset NPH is difficult to accurately diagnose and has not been reported in a cohort study. In this study, we assessed the genetic background and clinicopathologic features of adult NPH. METHODS: We investigated 18 sporadic adult patients who were suspected as having NPH by renal biopsy. We analyzed 69 genes that cause hereditary cystic kidney disease and compared clinicopathologic findings between patients with and without pathogenic mutations in NPH-causing genes. RESULTS: Seven of 18 patients had pathogenic NPH-causing mutations in NPHP1, NPHP3, NPHP4, or CEP164. Compared with patients without pathogenic mutations, those with pathogenic mutations were significantly younger but did not significantly differ in the classic NPH pathologic findings, such as tubular cysts. On the other hand, the number of tubules with thick tubular basement membrane (TBM) duplication, which was defined as >10-µm thickness, was significantly higher in patients with genetically proven adult NPH than in those without pathogenic mutations. α-Smooth muscle actin (α-SMA)-positive myofibroblasts were detected inside thick TBM duplication. CONCLUSIONS: In adult patients with NPH, thick TBM duplication was the specific finding. Our analysis also suggested that older patients tended to have no pathogenic mutations, even when they were suspected to have NPH by renal biopsy. These findings could be the novel clinical clue for the diagnosis of NPH in adult patients.

Sodium Hypochlorite is Effective against Biofilms in Dialysis Equipment.

To test the efficacy of chemical disinfectants against bacterial biofilms in hemodialysis equipment, a Center for Disease Control and Prevention (CDC)-Biofilm Reactor was used to create biofilms. Methylobacterium radiotolerance was isolated from the hemodialysis fluid and used as the test organism. We examined the efficacy of sodium hypochlorite (NaOCl) in elimination of planktonic cells compared to that in the case of biofilms. Planktonic bacteria were completely eliminated at 50 parts per million (ppm) of NaOCl, which is the lowest concentration for clinical use. The viable cell count in the biofilm reached its minimum value around a logarithmic reduction value (LRV) of 6, when the concentration was raised to 1000 ppm and the reaction time was extended by 1 hour or more. Furthermore, at 200 ppm, the LRV was elevated depending on the time. And the LRV while maintaining static conditions for 6 hours at 200 ppm was similar to that of short time at 1000 ppm. These results suggest that NaOCl has sufficient bactericidal activity even for biofilms at a practical concentration and reaction time, and that the CDC-Biofilm Reactor is an effective tool for finding useful disinfection conditions.

False-negative diagnosis of high anion gap in patients with end-stage kidney disease.

The traditional anion gap (AG) equation is widely used, but its misdiagnosis in end-stage kidney disease (ESKD) patients has not been investigated fully. Diagnostic accuracy to detect high AG was cross-sectionally evaluated using 3 AG equations in 1733 ESKD patients with an eGFR less than 15 mL/min/1.73 m2. The prevalence of high AG was 67.9%, 92.1% and 97.4% by the traditional, albumin-adjusted AG (aAG) and full AG equations, respectively. The sensitivity, specificity, accuracy and Kappa coefficient obtained with the traditional AG vs aAG equation were 0.70 vs 0.94, 0.98 vs 0.93, 0.7 vs 0.94, and 0.103 vs 0.44, respectively. Next, we created a subcohort comprising only patients with high full AG and investigated how the traditional AG equation leads to misdiagnoses. Multivariable-adjusted regression analysis in 1688 patients revealed that independent factors associated with a false-negative AG diagnosis were ARB use, eGFR, blood leukocyte count, serum chloride, bicarbonate, ionized calcium, potassium, albumin and phosphate. 93.2% of our subcohort prescribed any of RAAS inhibitors, Loop diuretics or Alkali which could increase either serum chloride or bicarbonate. Frequent use of these possible AG-reducing medications may conceal high AG state in patients with ESKD unless they have incidental inflammation which may increase AG value.

Remission of light chain proximal tubulopathy in IgG λ-type multiple myeloma by lenalidomide and dexamethasone therapy.

Light chain proximal tubulopathy is a rare manifestation of monoclonal gammopathy. A 73-year-old Japanese woman was noted to have urinary protein and hypertension on health examination and visited the regional clinic. She was noted to have IgG λ M protein and suspected of multiple myeloma. She was referred to us with massive proteinuria (7.5 g/g creatinine) and Bence Jones proteinuria without renal dysfunction. A renal biopsy revealed no glomerular abnormalities, but a tubular cast was observed partially in tubules without tubular atrophy or a crystalline structure. Direct Fast Scarlet staining was absent both in glomerulus and vascular wall. Immunofluorescence revealed λ light chain (LC) staining in the proximal tubules. Electron microscopy revealed nonspecific findings including increased lysosomes with irregular contours and mottled appearance. A bone marrow biopsy revealed plasma cell proliferation (35%) and multiple myeloma immunoglobulin G λ type. She showed progressive anemia and decrease of eGFR with elevated level of urinary ß-2 microglobulin. She was treated with lenalidomide + dexamethasone (Ld). With Ld therapy, she achieved hematologic and nephrologic remission reducing the free LC, λ/κ ratio, urinary protein level, and urinary ß-2 microglobulin level.

Detection Method for Aquatic Bacteria of the Fingers, as a Potential Origin of the Aqueous Solution Contamination.

　Aquatic bacteria were isolated from the hands of working staffs by an adapted culture protocol. When the sample solution obtained by the" glove juice method" was incubated for 3 days at room temperature, viable cell counts increased up to 105-fold, and the majority of the isolated colonies were shown to be Gram-negative aquatic bacteria, which carry the risk of contaminating water. Using R2A medium, coagulase-negative staphylococci were the dominant microbes immediately after recovery from the hands. Here it was revealed that bacteria of the phylum Proteobacteria isolated from the hand can be the causative bacteria of aqueous contamination. This modification in the GJ method may be useful as an effective training protocol to demonstrate the importance of hand hygiene and clean operation for aseptic manufacturing.

Acquired Factor V Inhibitors in a Patient with End-stage Renal Disease.

We report a case of acquired factor V inhibitors (AFVIs) in a patient with end-stage renal disease receiving warfarin therapy for atrial fibrillation. A 72-year-old Japanese man was admitted to our hospital complaining of tarry stools and abdominal pain. The laboratory findings revealed eosinophilia (52.1%), prolonged activated partial thromboplastin time (APTT) (98 s), PT (84 s), a factor V (FV) activity of <3%, and an FV inhibitor level of 6 Bethesda units/mL. After administration of prednisolone was started, his coagulation findings improved. However, his renal failure progressed, and he ultimately required chronic hemodialysis. This is the first case of AFVIs in a patient starting hemodialysis for end-stage renal disease.

Rapidly Progressive Renal Dysfunction in Two Elderly Patients with Renal Enlargement and Medullary Cystic Kidney Disease-like Acute Tubulointerstitial Injury.

Medullary cystic kidney disease (MCKD) is a hereditary disease associated with bilateral medullary polycysts and interstitial fibrosis. MCKD is typically associated with slowly progressive renal dysfunction. We herein report two rare elderly cases with enlarged kidneys and rapidly progressive renal dysfunction without myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), PR3-ANCA, or anti-glomerular basement membrane (GBM) antibodies. Renal biopsies revealed extensive tubular dilatation and atrophy with interstitial fibrosis consistent with MCKD. Both patients began hemodialysis therapy a few months later. Our cases suggest a MCKD subgroup among elderly patients with an undefined genetic background, rapidly progressive renal dysfunction, and enlarged kidneys.

Myeloperoxidase Antineutrophil Cytoplasmic Antibody (MPO-ANCA) Associated Crescentic and Necrotizing Glomerulonephritis (GN) with Membranoproliferative GN Features.

A 77-year-old man presented with a fever, non-productive cough, and edema formation. A laboratory analysis showed an elevated creatinine level (2.5 mg/dL), a high titer of myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) (99 U/mL), positive reaction for antinuclear antibody (×320), hematuria, and massive proteinuria (3.33 g/day). A renal biopsy revealed crescentic and necrotizing glomerulonephritis (GN) with membranoproliferative GN features [double contour appearance of the glomerular basement membrane, granular deposition of immunoglobulin (Ig) G, IgM, and C3 along the capillary wall, subendothelial and subepithelial deposits with mesangial interposition]. A potential relationship between MPO-ANCA associated GN and membranoproliferative GN is discussed.

[Association of blood pressure control effects on renal impairment with urinary protein: a study on the validity of the Japanese Society of Hypertension Guidelines for Management of Hypertension 2014].

BACKGROUND AND OBJECTIVE: Progression of chronic kidney disease (CKD) leads to the onset of cardiovascular dis- eases and an increase in the number of patients requiring dialysis initiation. In prder to promote the early detection and treatment of CKD, we assessed the effects of blood pressure control on renal impairment based on common test items and verified the usefulness of the target blood pressure for patients with CKD described in the Japanese Society of Hypertension Guidelines for the Management of Hypertension in 2014 (JSH 2014). SUBJECTS AND METHODS: Among patients who had been regularly visiting the outpatient clinic of Kasukabe Kisen Hospital for 24 months or more, 67 with a serum creatinine level of 1.2 mg/dL or higher were included in this study. Clinical blood pressure measurements obtained at the start of follow-up and at 6, 12, 18, and 24 months were averaged to serve as the 2-year mean blood pressure, and the progression rates of renal impairment were com- pared between patients achieving and those not achieving the target blood pressure of the JSH 2014. RESULTS: Among the diabetic patients with CKD, significant differences in renal impairment progression rates were observed between those achieving and those not achieving the target blood pressure. Among the non-diabetic patients with CKD, those achieving the target blood pressure tended to show slower progression of renal impair- ment, but their progression rates were not significantly different from those of the patients not achieving the target blood pressure. CONCLUSION: Blood pressure control is essential for patients with CKD. In patients with diabetes mellitus, the pro- gression rates of renal impairment can be substantially reduced by maintaining blood pressure below the target blood pressure described in the JSH 2014.

[A case of PR3-ANCA positive granulomatosis with polyangiitis recurrent with acute kidney injury after 7 years remission].

A 62-year-old-Japanese man had a history of probable granulomatosis with polyangiitis (GPA) from 7 years previously, showing kidney and vasculitis symptoms with PR3-ANCA (864 EU) without renal biopsy. Remission with normalization of renal function and urinary findings was induced by corticosteroid therapy. Prednisolone (PSL) was tapered to 5 mg/day and maintained for 6.5 years with a low positive titer of PR3-ANCA. After 7 years of remission, he was referred to our hospital because of arthralgia, fever, general fatigue and appetite loss with apparent urinary abnormality, increased serum Cr (1.8 mg/dL) and C reactive protein (CRP : 30.1 mg/dL). On admission, he showed a high titer of PR3-ANCA (> 300 U/mL). Renal biopsy demonstrated the existence of the pauci-immune type of severe crescentic necrotizing glomerulonephritis, tubulo-interstitial damage and perivascular granuloma. He was diagnosed as relapse of GPA (kidney-localized type) without upper respiratory tract (E) and lung (L) symptoms. Accordingly, he received steroid pulse therapy leading to improvement of these symptoms and renal function. Oral PSL at the dosage of 40 mg/day was administered after steroid pulse therapy, and then tapered to 20 mg/day. Cyclophosphamide was added within 8 weeks. He was discharged 8 weeks after treatment with a decreased level of Cr (1.5 mg/dL) and PR3-ANCA (244 U/mL). After discharge, PSL was tapered to 10 mg/day during the course of stability resulting in a further improved level of Cr (1.2 mg/dL), PR3-ANCA 40 U/mL in the outpatient clinic. In Japan, PR3-ANCA-positive GPA has a lower incidence than MPO-ANCA-positive microscopic vasculitis. In GPA, the kidney-localized (K) type without upper respiratory tract (E, L) symptoms is rare. Histologically, not only necrotizing crescentic glomerulonephritis but also perivascular granuloma in the kidney are very rare and interesting.

Expression of tight junction protein claudin-1 in human crescentic glomerulonephritis.

The origin of crescent forming cells in human glomerulonephritis (GN) remains unknown. Some animal studies demonstrated that parietal epithelial cells of Bowman's capsule (PECs) were the main component of proliferating cells and PEC-specific tight junction protein claudin-1 was expressed in crescentic lesions. We investigated the expression of claudin-1 in human GN. Immunohistochemistry for claudin-1 was performed on 17 kidney biopsy samples with crescent formation. Colocalization of claudin-1 with intracellular tight junction protein ZO-1 was also evaluated by immunofluorescence double staining. Claudin-1 is expressed mainly at the cell to cell contact site of proliferating cells in cellular crescentic lesions in patients with these forms of human GN. Small numbers of crescent forming cells showed extrajunctional localization of claudin-1. Colocalization of claudin-1 with ZO-1 was found at cell to cell contact sites of adjacent proliferating cells. In control samples, staining of claudin-1 was positive in PECs, but not in podocytes. Our findings suggest that claudin-1 contributes to crescent formation as a component of the tight junction protein complex that includes ZO-1. Co-localization of claudin-1 with ZO-1 implies the formation of functional tight junction complexes in crescentic lesions to prevent the interstitial damage caused by penetration of filtered molecules from Bowman's space.

A Case of Membranous Glomerulonephropathy Associated with Takayasu's Arteritis.

Glomerulonephropathy is a rare complication of Takayasu's arteritis (TA). To date, most glomerulonephropathies associated with TA show the histological feature of mesangial proliferation. Membranous glomerulonephropathy (MG) is a form of glomerulonephropathy in which the mesangial proliferation is not conspicuous and its association with TA is extremely rare. A 54-year-old man was referred to our hospital due to progressive edema in the lower limbs and nephrotic range proteinuria. Five years previously, he underwent percutaneous angioplasty for left subclavian artery stenosis. Kidney biopsy revealed stage II MG. General examination including enhanced CT scan confirmed the presence of TA. He started oral prednisolone therapy at a dose of 40 mg daily. The C-reactive protein level normalized 7 days after the prednisolone therapy. Three months later, proteinuria had remitted. Though the true relationship between MG and TA was not revealed in present case, considering the fact that complete remission of nephrotic syndrome occurred following the improvement of C-reactive protein level in response to steroid therapy, TA might be the secondary cause of MG. To our best knowledge, only two case reports described the association of MG and TA previously. Those two patients, however, also demonstrated the feature of systemic lupus erythematosus in addition to TA. This is the first case report that describes a patient who presented as MG associated with TA, but not complicated by systemic lupus erythematosus.