Efficacy of dotinurad in patients with severe renal dysfunction.

BACKGROUND: Although hyperuricemia is associated with the progression of chronic kidney disease (CKD), a reduction in CKD progression by uric acid (UA)-lowering therapy has been controversial. Recently, dotinurad, a uricosuric drug with selective urate reabsorption inhibitory properties, has been developed. However, its efficacy in lowering serum UA levels and its effects on renal function in patients with severe renal dysfunction are unclear. Thus, this study aimed to determine the effects of dotinurad on renal function in patients with severe renal dysfunction. METHODS: Data from 53 outpatients with hyperuricemia who newly received dotinurad between December 2020 and October 2022 were retrospectively analyzed. The mean baseline estimated glomerular filtration rate (eGFR) was 38.7 ± 17.0 mL/min/1.73 m2. The patients were divided into three groups based on their baseline eGFR: eGFR < 30 (n = 17), 30 ≤ eGFR < 45 (n = 17), and eGFR ≥ 45 (n = 19). RESULTS: The mean follow-up period was 9.8 ± 4.5 (range, 3-21) months. Serum UA levels significantly decreased in all groups. Although eGFR did not significantly change in patients with 30 ≤ eGFR < 45 and eGFR ≥ 45 (P = 0.918 and P = 0.535, respectively), it improved significantly in patients with eGFR < 30 (P = 0.032). The proportion of patients with improved eGFR was significantly higher in patients with eGFR < 30 (P = 0.038) than in patients with 30 ≤ eGFR < 45 and eGFR ≥ 45. In the multivariate logistic regression analysis, baseline eGFR < 30 and achieving a serum UA level of ≤ 6.0 mg/dL were significantly associated with improved eGFR (P = 0.033 and P = 0.015, respectively). CONCLUSIONS: Dotinurad may have UA-lowering effects and the potential to improve kidney function in patients with severe renal dysfunction.

Use of the Japanese Version of the Montreal Cognitive Assessment to Estimate Cognitive Decline in Patients Aged 75 Years or Older with and without Type 2 Diabetes Mellitus.

BACKGROUND: The number of people diagnosed with dementia worldwide is set to increase significantly. Patients with dementia often have comorbidities, particularly diabetes, and patients with type 2 diabetes mellitus (T2DM) have a high risk of cognitive decline. This study investigated whether older people with T2DM have disease-specific cognitive deficits. METHODS: The Montreal Cognitive Assessment is a well-known tool for examining mild cognitive impairment, and the modified Japanese version (MoCA-J) has been confirmed as effective. Using the MoCA-J, we assessed the cognitive function of Japanese adults aged ≥75 years with and without T2DM and analyzed the results. RESULTS: Thirty-three patients with T2DM and 23 non-DM patients completed the examination, and MoCA-J total scores differed between these groups (T2DM mean, 21.4 ± 3.5; non-DM mean, 23.5 ± 3.6). Only 9% of patients with T2DM and 39% of those with non-DM had scores ≥26, which is the cutoff point for mild cognitive impairment, although all patients were capable of self-care. Additionally, delayed recall scores were significantly lower for the older patients with T2DM had for the non-DM group. CONCLUSIONS: Patients aged ≥75 years with T2DM might have worse cognition than those without T2DM; the inability to perform delayed recall in T2DM patients suggests a decline in cognitive function. Therefore, patients aged ≥75 years with T2DM should receive explanations of their care that are individualized in relation to their cognitive status.

Effects of Renal Function on Urinary Excretion and Serum Concentration of Uric Acid in Patients Treated with Febuxostat for Chronic Kidney Disease.

BACKGROUND: Febuxostat is recommended for lowering serum uric acid (sUA) concentration in chronic kidney disease (CKD) patients with hyperuricemia. However, it remains uncertain how febuxostat affects associations between several laboratory variables related to glomerular filtration and renal tubular reabsorption of uric acid. METHODS: We retrospectively analyzed the records of 148 patients with CKD and hyperuricemia: 122 were treated with febuxostat, and 26 were not. Clinical and laboratory variables were used to calculate estimated glomerular filtration rate (eGFR), fractional excretion of uric acid (FEUA), and estimated 24-h urinary excretion of uric acid (eEUA). We examined correlations of those variables and compared patients who did and did not receive febuxostat. RESULTS: eGFR and FEUA were significantly inversely regardless of febuxostat-treatment status. eGFR was significantly inversely correlated with sUA in patients who received febuxostat, but not in those who did not. Similarly, there was a significant positive correlation between FEUA and eEUA only in patients treated with febuxostat. CONCLUSIONS: FEUA increased as eGFR decreased in our patients. Febuxostat changed correlation patterns for clinical and laboratory variables. Additional administration of uricosuric agents might help further lower sUA by increasing FEUA and eEUA in patients treated with febuxostat.

Low-Density Lipoprotein Apheresis in Patients with Acute Kidney Injury Due to Minimal Change Disease Requiring Acute Renal Replacement Therapy.

Low-density lipoprotein apheresis (LDL-A) has been developed as a therapy for familial hypercholesterolemia, but LDL-A has also been used as a general treatment for drug-resistant nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS). The patients with NS due to minimal change disease (MCD) are often difficult to control effective circulating plasma volume, causes acute kidney injury (AKI), and when diuretics are not effective and the respiratory condition of patients worsens, patients require acute renal replacement therapy (ARRT). The effectiveness of LDL-A is not only reduction of serum low-density lipoprotein but also various other benefits. LDL-A might have improved renal hemodynamics by reducing vasoconstrictive eicosanoids and contributed to the therapeutic effect of antiproteinuric drugs such as corticosteroids. We treated a 49-year-old Japanese woman and a 71-year-old Japanese man with AKI caused by NS due to MCD, who required ARRT. Although these patients received ARRT and corticosteroids, their AKI and MCD did not improve sufficiently. We initiated LDL-A treatment for these patients as an additional treatment modality, because their total serum cholesterol levels were high at the time of admission. After the additional LDL-A treatment, both patients were able to discontinue ARRT, because NS and AKI in both patients were improved sufficiently. It is possible that early additional LDL-A is effective for patients with AKI and NS due to MCD who require ARRT, and may help patients discontinue ARRT because of the effect of LDL-A such as improving hypercoagulability and renal hemodynamics and contributing to the therapeutic effect of corticosteroids.

A case of membranous nephropathy diagnosed with lupus nephritis 11 years after onset.

A 34-year-old female patient presented to our hospital with lower extremity edema and proteinuria during pregnancy. Renal biopsy was performed and the patient was diagnosed with nephrotic syndrome due to lupus-like membranous nephropathy. This diagnosis was reached upon as laboratory findings upon admission, wherein both anti-nuclear and anti-double-stranded DNA antibodies revealed negative, did not fulfill the criteria for systemic lupus erythematosus (SLE) proposed by the American College of Rheumatology (ACR) and the patient did not reveal any typical physical manifestations of SLE. Methylprednisolone pulse therapy was started followed by oral administration of prednisolone. Urinary protein excretion diminished after 1 year of treatment. Eleven years later, the same patient was admitted to our hospital again with relapse of nephrotic syndrome. Laboratory findings upon second admission, wherein both anti-nuclear and anti-double-stranded DNA antibodies revealed positive, fulfilled the ACR criteria. Renal biopsy was performed again, resulting in a diagnosis of lupus nephritis. Steroid therapy combined with administration of mycophenolate mofetil led to an incomplete remission. Immunofluorescence studies confirmed the presence of IgG, IgM, C3, and C1q in renal biopsy specimens both at first and second admissions. Furthermore, immunofluorescence studies confirmed the presence of IgG1-4 in the first biopsy and tubuloreticular inclusions (TRIs) were revealed using electron microscopy. The present case represents the possibility that characteristic pathological findings of lupus nephritis, including TRIs, can reveal themselves before a diagnosis of SLE.

Correlation between Pathological Findings and the Usefulness of Clinical Guidelines for the Treatment of ANCA-Positive RPGN: A Retrospective Analysis.

BACKGROUND: The physical condition of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated rapidly progressive glomerulonephritis (RPGN) is at times too critical for physicians to undertake a renal biopsy. In such cases, physicians need to start treatments without determining the pathological features of the disease. However, the prevalent clinical practice guidelines for ANCA-associated RPGN in Japan do not necessitate the pathological findings in a renal biopsy for determining first-line treatments. The aim of this study was to assess the correlation between the pathological findings and the clinical guideline-based treatments of ANCA-associated RPGN. METHODS: We investigated clinical and pathological features of patients who were admitted to our hospital to undergo a percutaneous renal biopsy for the diagnosis of ANCA-associated RPGN and were treated per clinical practice guidelines formulated by the Japanese Society of Nephrology. We divided patients into the following three groups according to their treatments: (a) group A, oral intake of prednisolone (PSL) only; (b) group B, methylprednisolone (mPSL) pulse therapy followed by oral intake of PSL; and (c) group C, mPSL pulse therapy followed by oral intake of PSL and the administration of immunosuppressive agents. We compared the crescent formation ratio (CFR) in glomeruli in each treatment group. RESULTS: The median CFR (%; ±standard deviation [SD]) in group A (8.7%±7.7%) was significantly lower than that in groups B (30.2%±15.7%) and C (71.3%±25.5%); group A vs. group B, P<0.05; group A vs. group C, P<0.0001. In addition, the median CFR in group B was significantly lower than that in group C (P<0.01). The median serum creatinine levels (mg/dL; ±SD) in both groups A (2.03±0.96 mg/dL) and B (1.90±0.86 mg/dL) were significantly lower than that in group C (4.30±1.63 mg/dL); group A vs. group C, P<0.01; group B vs. group C, P<0.01. No significant difference was observed in the serum levels of C-reactive protein and ANCA in each treatment group. Although the pathological features of renal biopsy are not included in the factors in the clinical scores described in the guidelines, guideline-based treatments reflected the severity of the crescent formation in each treatment group. CONCLUSIONS: This study suggests that the clinical practice guidelines for ANCA-associated RPGN used in Japan facilitate physicians to determine disease management in patients presenting difficulties in undergoing a renal biopsy.

A Case of Sjögren's Syndrome Complicated with Interstitial Nephritis and Delayed Onset Autoimmune Hepatitis.

A 61-year-old woman was admitted to our hospital because of muscle paralysis and was found to have severe hypokalemia. A gallium-67 scintigram revealed a positive accumulation in the bilateral salivary glands, and a labial minor salivary gland biopsy demonstrated a massive lymphocyte infiltrate around the salivary ducts. She was diagnosed with Sjögren's syndrome (SS) associated with renal tubular acidosis. Renal biopsy revealed tubulointerstitial nephritis with a mild focal infiltration of lymphocytes and plasma cells. These pathological features were compatible with SS with renal involvement. Acidosis and hypokalemia were corrected with sodium bicarbonate and potassium chloride, which relieved the patient's symptoms. Although steroid therapy has been reported to be effective in SS-associated tubulointerstitial nephritis, the patient's serum potassium level could be controlled without administering steroids during the first admission. Five years later, she was admitted again because of severe liver dysfunction attributed to autoimmune hepatitis. Oral administration of prednisolone resulted in the normalization of her transaminase levels, and the control of her serum potassium level became easier. It has been reported that patients with SS with salivary gland involvement tend to have hepatic complications, and those with hepatic complications tend to have renal involvement. Physicians should be aware of hepatic involvement, even if there is no liver dysfunction at the initial diagnosis of SS with salivary gland and renal involvement. It remains uncertain whether the administration of a low dose of steroids before the onset of autoimmune hepatitis might have prevented the development of liver dysfunction in our patient.

A Case of Anti-Glomerular Basement Membrane Antibody-Positive Systemic Lupus Erythematosus with Pulmonary Hemorrhage Successfully Treated at an Early Stage of the Disease.

We report here a case of systemic lupus erythematosus (SLE) with pulmonary hemorrhage and anti-glomerular basement membrane (anti-GBM) antibodies. A 42-year-old woman was admitted to our hospital with complaints of exanthema, arthralgia, shortness of breath, and hemoptysis. Plain chest computed tomography (CT) scan revealed pericardial effusion, bilateral pleural effusions, and pulmonary hemorrhage. Laboratory findings on admission revealed proteinuria, microscopic hematuria, anemia, leukopenia, hypoalbuminemia, hypocomplementemia, and slightly elevated levels of serum creatinine. Serological tests revealed elevated titers of serum anti-GBM antibodies, proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCA), and anti-double stranded deoxyribonucleic acid (dsDNA)-immunoglobulin G (IgG) antibodies. Early treatment with steroid pulse therapy combined with plasma exchange resolved the patient's pulmonary hemorrhage and renal dysfunction. Renal biopsy carried out after the treatment revealed a recovery phase of acute tubular injury with minor glomerular abnormalities without linear IgG deposition along the GBMs. For a good prognosis, it is necessary to start treatment immediately in patients with anti-GBM antibody-positive SLE associated with pulmonary hemorrhage.

A case of monoclonal immunoglobulin G1-lambda deposition associated with membranous feature in a patient with hepatitis C viral infection.

A 63-year-old man with hepatitis C virus infection was admitted to our hospital for nephrotic syndrome. Light microscopic analysis of a percutaneous renal biopsy showed thickening of the glomerular capillary walls and spike formation. Immunofluorescence revealed granular deposition of monoclonal immunoglobulin G1-lambda and C3 complement along the glomerular basement membrane. Urinary protein excretion decreased slightly after combined treatment with steroid and an immunosuppressive agent. Monoclonal immunoglobulin deposition disease with membranous feature is rare. Additional reports of such cases are needed to elucidate the mechanisms and optimal therapy for this rare entity.

Catalytic wet oxidation of o-chlorophenol at mild temperatures under alkaline conditions.

Wet oxidation of a 100 ppm aqueous solution of o-chlorophenol (o-CP) was performed in a lab-scale batch reactor using 3% Ru/TiO(2) catalyst at 373 and 413 K, and a partial oxygen pressure of 0.1 MPa. The experiments were conducted by varying the initial pH values of o-CP solution from pH 6.3 to 9.8 and 11.8. From the results, it was revealed that the catalytic decomposition of o-CP occurred most effectively at 413 K and at the initial pH of 9.8. Complete decomposition and dechlorination of o-CP were almost achieved within 1h, and about 85% of TOC was removed in 3.0 h. On the other hand, the catalytic wet oxidation of o-CP at a higher pH value of 11.8 was not effective in the removal of TOC. The incomplete removal of TOC at the initial pH of 11.8 is likely attributed to a low pK(a) of carboxylic acids formed during the wet oxidation of o-CP.

[A single case report of postrenal acute renal failure caused by pelvic and ureteral tumor composed of a mixture of transitional cell carcinoma and adenocarcinoma].

A 68-year-old woman was admitted to our hospital because of severe oliguria and macrohematuria. She was diagnosed as postrenal acute renal failure, because of bilateral dilatation of the renal pelvis on abdominal computed tomography (CT). Percutaneous nephrostomy was performed after hemodialysis was initiated. Next, urinary volume and serum creatinine level were normalized. Percutaneous biopsy towards the mass in the peritoneal cavity under abdominal CT revealed adenocarcinoma, although the primary site of the carcinoma could not be identified. Autopsy was permitted after her sudden death. It revealed that the primary carcinoma was a right pelvic and ureteral tumor. The right pelvic and ureteral tumor was composed of a mixture of transitional cell carcinoma and adenocarcinoma.