Kidney Biopsy Proven Thrombotic Microangiopathy Induced by Methamphetamine: A Case Report.

A 47-year-old man was admitted to our hospital with acute kidney injury, severe hypertension, heart failure, thrombocytopenia, and elevated lactate dehydrogenase. Renal biopsy revealed fibrin thrombi within the glomerular capillaries and moderate fibrotic intimal thickening in the interlobular arteries. The histological diagnosis was thrombotic microangiopathy (TMA). Regarding cardiac involvement, we found marked stenosis in the left anterior descending artery on coronary angiography and cardiomyopathy on myocardial biopsy. Blood concentrations of amphetamine and methamphetamine were high (14.1 ng/mL and 333 ng/mL, respectively). It is important to consider methamphetamine as a cause of renal TMA and multi-organ dysfunction.

Infection-Related Cryoglobulinemic Glomerulonephritis with Serum Anti-Factor B Antibodies Identified and Staining for NAPlr/Plasmin Activity Due to Infective Endocarditis.

In this rare case of infection-related cryoglobulinemic glomerulonephritis with infective endocarditis, a 78-year-old male presented with an acute onset of fever and rapidly progressive glomerulonephritis. His blood culture results were positive for Cutibacterium modestum, and transesophageal echocardiography showed vegetation. He was diagnosed with endocarditis. His serum immunoglobulin M, IgM-cryoglobulin, and proteinase-3-anti-neutrophil cytoplasmic antibody levels were elevated, and his serum complement 3 (C3) and C4 levels were decreased. Renal biopsy results showed endocapillary proliferation, mesangial cell proliferation, and no necrotizing lesions on light microscopy, with strong positive staining for IgM, C3, and C1q in the capillary wall. Electron microscopy showed deposits in the mesangial area in the form of fibrous structures without any humps. Histological examination confirmed a diagnosis of cryoglobulinemic glomerulonephritis. Further examination showed the presence of serum anti-factor B antibodies and positive staining for nephritis-associated plasmin receptor and plasmin activity in the glomeruli, suggesting infective endocarditis-induced cryoglobulinemic glomerulonephritis.

Intraoperative hemodialysis during open-heart surgery in patients with severe chronic kidney disease: a retrospective cohort study.

BACKGROUND: Acute kidney injury and chronic kidney disease (CKD) after cardiac surgery are associated with poor renal prognosis and increased mortality. The impact of intraoperative hemodialysis (IHD) on postoperative renal function remains unknown. We aimed to evaluate the utility of IHD during open-heart surgery in patients with severe non-dialysis-dependent chronic kidney disease (CKD-NDD) and its association with clinical outcomes. METHODS: This was a single-center retrospective cohort study that employed IHD during non-emergency open-heart surgery in patients with CKD stage G4 or G5. Patients who underwent emergent surgery, chronic dialysis, and/or kidney transplantation were excluded. We retrospectively compared the clinical characteristics and outcomes between patients from the IHD and non-IHD groups. The primary outcomes were 90-day mortality and postoperative initiation of renal replacement therapy (RRT). RESULTS: Twenty-eight patients were categorized into the IHD group and 33 into the non-IHD group. When comparing the IHD and non-IHD groups, men accounted for 60.7 vs. 50.3% of patients, the mean patient age was 74.5 (standard deviation [SD] 7.0) vs. 72.9 (SD 9.4) years (p = 0.744), and the proportion of patients with CKD G4 was 67.9 vs. 84.9% (p = 0.138). Regarding clinical outcomes, no significant differences were observed in the 90-day mortality (7.1 vs. 3.0%; p = 0.482) and 30-day RRT (17.9 vs. 30.3%; p = 0.373) rates between the groups. Among the patients with CKD G4, the IHD group had significantly lower 30-day RRT rates than the non-IHD group (0 vs. 25.0%; p = 0.032). RRT initiation was less likely for patients with CKD G4 (odds ratio 0.07, 95% confidence interval [CI] 0.01-0.37; p = 0.002); however, IHD did not significantly decrease the incidence of poor clinical outcomes (odds ratio 0.20, 95% CI 0.04-1.07; p = 0.061). CONCLUSIONS: IHD during open-heart surgery in patients with CKD-NDD did not improve their clinical outcomes with regards to postoperative dialysis. However, for patients with CKD G4, IHD may be useful for postoperative cardiac management.

Machine learning for morbid glomerular hypertrophy.

A practical research method integrating data-driven machine learning with conventional model-driven statistics is sought after in medicine. Although glomerular hypertrophy (or a large renal corpuscle) on renal biopsy has pathophysiological implications, it is often misdiagnosed as adaptive/compensatory hypertrophy. Using a generative machine learning method, we aimed to explore the factors associated with a maximal glomerular diameter of ≥ 242.3 µm. Using the frequency-of-usage variable ranking in generative models, we defined the machine learning scores with symbolic regression via genetic programming (SR via GP). We compared important variables selected by SR with those selected by a point-biserial correlation coefficient using multivariable logistic and linear regressions to validate discriminatory ability, goodness-of-fit, and collinearity. Body mass index, complement component C3, serum total protein, arteriolosclerosis, C-reactive protein, and the Oxford E1 score were ranked among the top 10 variables with high machine learning scores using SR via GP, while the estimated glomerular filtration rate was ranked 46 among the 60 variables. In multivariable analyses, the R2 value was higher (0.61 vs. 0.45), and the corrected Akaike Information Criterion value was lower (402.7 vs. 417.2) with variables selected with SR than those selected with point-biserial r. There were two variables with variance inflation factors higher than 5 in those using point-biserial r and none in SR. Data-driven machine learning models may be useful in identifying significant and insignificant correlated factors. Our method may be generalized to other medical research due to the procedural simplicity of using top-ranked variables selected by machine learning.

Use of Immunosuppressive Therapy in the Treatment of IgA-dominant Infection-related Glomerulonephritis.

A 51-year-old Japanese man who experienced colon cancer recurrence following primary and metastatic lesion resection was hospitalized due to facial cellulitis with febrile neutropenia and purpura on his lower extremities after chemotherapy. It was complicated by rapidly progressive glomerulonephritis. He was diagnosed with immunoglobulin A (IgA)-dominant endocapillary proliferative glomerulonephritis based on kidney histology. His glomeruli were positive for the nephritis-associated plasmin receptor, plasmin activity and galactose-deficient IgA1 (Gd-IgA1). A skin biopsy immunofluorescence study revealed IgA deposition within perivascular regions but no Gd-IgA1 deposition. The final diagnosis was IgA-dominant infection-related glomerulonephritis (IRGN). The patient's renal function returned to normal after receiving immunosuppressive therapy that consisted of a glucocorticoid and a cyclophosphamide. Immunosuppressive therapy should be considered in cases of IRGN if the patient's infection is completely under control.

Maximum Glomerular Diameter and Oxford MEST-C Score in IgA Nephropathy: The Significance of Time-Series Changes in Pseudo-R2 Values in Relation to Renal Outcomes.

The progression of immunoglobulin A nephropathy (IgAN) is currently assessed using the Oxford MEST-C score, which uses five indicators (mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents) but has not yet included any risk factors related to glomerular size. Therefore, we tested whether adding another indicator, maximal glomerular diameter (Max GD), would improve the prognostic ability of this scoring system. The data of 101 adult patients diagnosed with IgAN between March 2002 and September 2004 were reviewed. We used McFadden's pseudo-R2 and the corrected Akaike information criterion to assess model fit and the concordance (C)-statistic to assess discriminatory ability. A 10 µm increase in Max GD was significantly associated with a composite outcome (≥50% decline in the estimated glomerular filtration rate or end-stage renal disease). The receiver operating characteristic analysis determined the cut-off for high vs. low Max GD at 245.9 µm, and adding high Max GD to the MEST-C score significantly improved the model's discrimination of renal outcomes at 5 and ≥10 years. Thus, including the Max GD in the Oxford classification of IgAN might increase its robustness and provide a more comprehensive prognostic system for clinical settings.

Successful entecavir plus prednisolone treatment for hepatitis B virus-associated membranoproliferative glomerulonephritis: A case report.

RATIONALE: Adult-onset hepatitis B virus-associated membranoproliferative glomerulonephritis (HBV-MPGN) is generally refractory, and an effective treatment for this condition has not been established. The indications for steroids in HBV-MPGN are an important clinical concern. PATIENT CONCERNS: A 28-year-old woman with a chronic hepatitis B virus infection developed nephrotic syndrome in her second month of pregnancy, with urinary protein levels of 3 to 10 g/d that continued into her postpartum period. She was a carrier of HBV with HBeAg seroconversion. As her renal impairment could have been a result of pregnancy, we observed her for 10 months postpartum without any intervention. However, spontaneous remission after childbirth was not achieved and urine protein levels were sustained at 1 to 3 g/d. About 10 months after delivery, elevated serum liver enzyme levels were observed. DIAGNOSIS: Biopsies showed MPGN, with deposition of hepatitis B antigen in the glomeruli, and chronic B-type hepatitis with a severity grade of A1F0. She was diagnosed with HBV-MPGN. INTERVENTIONS: The patient was started on entecavir 0.5 mg/d in March 2008. Within 1 month, serum HBV DNA became undetectable; within 3 months, her alanine aminotransferase levels normalized. However, urinary protein excretion did not decrease to <2 g/d. On a second renal biopsy, performed 7 months after entecavir treatment, proliferative lesions of the glomeruli were observed; therefore, prednisolone was started at an initial dose of 30 mg/d. OUTCOMES: Her proteinuria improved immediately and prednisolone was tapered over 10 months. A third renal biopsy showed a remarkable resolution of HBV-MPGN, with a significant decrease in mesangial proliferation and immune complex deposition. HBV reactivation was not observed during the prednisolone treatment. LESSONS: Additional prednisolone therapy in combination with antiviral therapy should be considered for refractory HBV-MPGN, with sufficient care taken regarding HBV reactivation.

Biopsy-proven vancomycin-induced acute kidney injury: a case report and literature review.

BACKGROUND: Vancomycin is the first-line antibiotic for methicillin-resistant Staphylococcus aureus and coagulase-negative strains. The risk of vancomycin-induced acute kidney injury increases with plasma vancomycin levels. Vancomycin-induced acute kidney injury is histologically characterized by acute interstitial nephritis and/or acute tubular necrosis. However, only 12 biopsy-proven cases of vancomycin-induced acute kidney injury have been reported so far, as renal biopsy is rarely performed for such cases. Current recommendations for the prevention or treatment of vancomycin-induced acute kidney injury are drug monitoring of plasma vancomycin levels using trough level and drug withdrawal. Oral prednisone and high-flux haemodialysis have led to the successful recovery of renal function in some biopsy-proven cases. CASE PRESENTATION: We present the case of a 41-year-old man with type 1 diabetes mellitus, who developed vancomycin-induced acute kidney injury during treatment for Fournier gangrene. His serum creatinine level increased to 1020.1 µmol/L from a baseline of 79.6 µmol/L, and his plasma trough level of vancomycin peaked at 80.48 µg/mL. Vancomycin discontinuation and frequent haemodialysis with high-flux membrane were immediately performed following diagnosis. Renal biopsy showed acute tubular necrosis and focal acute interstitial nephritis, mainly in the medullary rays (medullary ray injury). There was no sign of glomerulonephritis, but mild diabetic changes were detected. He was discharged without continuing haemodialysis (serum creatinine level, 145.0 µmol/L) 49 days after initial vancomycin administration. CONCLUSIONS: This case suggests that frequent haemodialysis and renal biopsy could be useful for the treatment and assessment of vancomycin-induced acute kidney injury, particularly in high-risk cases or patients with other renal disorders.

Overweight and obesity accelerate the progression of IgA nephropathy: prognostic utility of a combination of BMI and histopathological parameters.

BACKGROUND: Although more than 40 years have passed since IgA nephropathy (IgAN) was first reported, predicting the renal outcome of individual IgAN patients remains difficult. Emerging epidemiologic evidence indicates that overweight and obesity are risk factors for end-stage renal disease. We aimed to elucidate the outcome of overweight IgAN patients and improve our ability to predict the progression of IgAN based on a combination of body mass index (BMI) and histopathological parameters, including maximal glomerular area (Max GA). METHODS: Forty-three adult IgAN patients whose estimated glomerular filtration rate was ≥50 ml/min/1.73 m(2) were enrolled in this study. Renal biopsy specimens were evaluated according to the Oxford classification of IgAN. A Kaplan-Meier analysis and the multivariate Cox proportional hazards method were used to evaluate 10-year kidney survival and the impact of covariates. The ability of factors to predict the progression of IgAN was evaluated by their diagnostic odds ratio (DOR). RESULTS: A BMI ≥25 kg/m(2) was found to be an independent predictor of a ≥1.5-fold increase in serum creatinine value (DOR 7.4). The combination of BMI ≥25 kg/m(2), Max GA ≥42,900 µm(2), and presence of mesangial hypercellularity (Oxford M1) optimally raised predictive power for disease progression of IgAN (DOR 26.0). CONCLUSION: A combination of BMI ≥25 kg/m(2), the Oxford classification M1, and a Max GA ≥42,900 µm(2) can serve as a predictor of long-term renal outcome of IgAN.

Maximal glomerular diameter as a 10-year prognostic indicator for IgA nephropathy.

BACKGROUND: Although there have been many reports on clinicopathological studies of immunoglobulin A nephropathy (IgAN), reliable outcome predictors are still lacking. We therefore assessed maximal glomerular diameter (Max GD), an indicator of glomerular size, as a predictor of the long-term evolution of renal histopathology. METHODS: Forty-three adult patients, diagnosed with IgAN, who had estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m(2), were enrolled in this study. Prognostic variables for renal survival were examined by using the multivariate Cox proportional hazards method. The optimal cut-off value of Max GD was 242.3 µm (AUC = 0.78, sensitivity = 62.5%, specificity = 81.5%) by using receiver operating characteristics analysis. In order to assess the characteristics of glomerular hypertrophy, we divided the cases into two groups according to the Max GD value (Group A, ≥242 µm; Group B, <242 µm). Renal survival was also assessed by Kaplan-Meier curves with the log-rank test. RESULTS: The Max GD was significantly correlated with age, body mass index and serum triglyceride levels at the time of renal biopsy. During the 10-year follow-up period, the Max GD was significantly correlated with eGFR decline per year, and proteinuria, but not with hematuria. A multiple regression analysis by the Cox method adjusted for age, sex and eGFR showed that the Max GD values were significantly associated with a 1.5-fold increase in serum creatinine (Cr) values (hazard ratio = 1.04, P = 0.03). Renal function in 66.7% of the patients whose Max GD was ≥242 µm had at least a 1.5-fold increase in their serum Cr value at the 10-year follow-up examination (log-rank, P = 0.003). CONCLUSIONS: The results of this study suggest that Max GD is a simple quantitative prognostic indicator of the disease progression in IgAN patients.

[Case of membranous nephropathy associated with argyria].

We experienced a case of membranous nephropathy associated with argyria. The patient was a 78-year-old woman who had noticed blue skin of the face and azure lunulae for 8 years. She was admitted to our hospital for edema and proteinuria. She was diagnosed as membranous nephropathy by needle renal biopsy, and treated with prednisolone. Her proteinuria disappeared after 63 days. We investigated the blue skin of her face and azure lunulae. Skin biopsy was performed and black granules deposited in the upper layer of the corium were observed. The granules were identified with silver by EDS (energy-dispersive X-ray spectroscopy) analysis. Membranous nephropathy associated with gold or mercury has been reported, but association with silver has not been reported. We considered that this is a rare case of membranous nephropathy associated with silver.

Effect of mineralocorticoid deficiency on ion and urea transporters and aquaporin water channels in the rat.

Mineralocorticoid deficiency is associated with impaired urinary concentration and dilution. The present investigation was undertaken to determine the effects of selective mineralocorticoid deficiency on renal sodium and urea transporters and aquaporin water channels and whether these perturbations can be reversed by maintenance of extracellular fluid volume. Mineralocorticoid deficiency was induced by bilateral adrenalectomies with glucocorticoid replacement. Mineralocorticoid deficient rats receiving plain drinking water (MDW) were compared with mineralocorticoid deficient rats receiving saline-drinking water (MDS) in order to maintain extracellular fluid volume, and with controls (CTL). In MDW rats, there was a significant decrease in renal outer medulla Na-K-2Cl co-transporter and outer medulla Na-K-ATPase as well as an increase in inner medulla aquaporins 2 and 3. There were no significant changes in aquaporin-1, aquaporin-4, or urea transporters. These alterations were reversed with maintenance of extracellular fluid volume in MDS rats. Our findings indicate that mineralocorticoid deficiency in the rat is associated with alterations in factors involved in the countercurrent concentrating mechanism (Na-K-2Cl, Na-K-ATPase) and osmotic water equilibration in the collecting duct (AQP2, AQP3). Maintenance of sodium balance and extracellular fluid volume is associated with normalization of these perturbations.