Association of hyperphosphatemia with renal prognosis in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Serum phosphate (P) levels are generally lower in autosomal dominant polycystic kidney disease (ADPKD) than in other kidney disorders, potentially masking the clinical significance of hyperphosphatemia. This study aimed to determine if serum P levels can predict renal outcomes in ADPKD patients. METHODS: We included 235 patients with ADPKD who were not taking drugs to treat hyperphosphatemia. Survival analysis was performed for the renal outcome of a 50% reduction in estimated glomerular filtration rate or initiation of renal replacement therapy. RESULTS: Multivariable Cox regression analyses revealed that serum P (1 mg/dL increase, HR = 2.03, P < 0.0001) was a significant risk factor for kidney disease progression. Similarly, hyperphosphatemia (P > 3.5 mg/dL, HR = 2.05; P > 4.0 mg/dL, HR = 1.90; P > 4.5 mg/dL, HR = 2.78; P > 5.0 mg/dL, HR = 27.22) was significantly associated with renal prognosis. Kaplan-Meier analysis showed significantly lower kidney survival rates in patients with P > 3.5 mg/dL than in those without hyperphosphatemia (log-rank test, P < 0.0001), and similar Kaplan-Meier analysis results were found for P > 4.0 mg/dL, P > 4.5 mg/dL, and P > 5.0 mg/dL. The 2 year kidney survival rate for ADPKD patients with P > 3.5 mg/dL was 66.7% overall and 41.4% in those with stage 4-5 CKD. For patients with P > 4.0 mg/dL, the survival rate dropped to 46.8% overall and 28.2% in those with stage 4-5 CKD, indicating a very poor prognosis. CONCLUSION: Hyperphosphatemia was associated with renal prognosis in patients with ADPKD. In these patients, attention should be paid to even mild serum P elevation of > 3.5 or > 4.0 mg/dL.

PLA2R-positive membranous nephropathy in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases. CASE PRESENTATION: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy. CONCLUSIONS: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.

Factors associated with early-onset intracranial aneurysms in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Recently, the importance of attribute-based medicine has been emphasized. The effects of early-onset intracranial aneurysms on patients can be significant and long-lasting. Herein, we compared the factors associated with intracranial aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD) according to age categories (≥ 50 years, < 50 years). METHODS: We included 519 ADPKD patients, with a median age of 44 years, estimated glomerular filtration rate of 54.5 mL/min/1.73 m2, and total follow-up duration of 3104 patient-years. Logistic regression analyses were performed to determine factors associated with intracranial aneurysms. RESULTS: Regarding the presence of intracranial aneurysm, significant interactions were identified between the age category (age ≥ 50 years), female sex (P = 0.0027 for the interaction) and hypertension (P = 0.0074 for the interaction). Female sex and hypertension were associated with intracranial aneurysm risk factors only in patients aged ≥ 50 years. The presence of intracranial aneurysm was significantly associated with chronic kidney disease (CKD) stages 4-5 (odds ratio [OR] = 3.87, P = 0.0007) and family history of intracranial aneurysm or subarachnoid hemorrhage (OR = 2.30, P = 0.0217) in patients aged < 50 years. For patients aged ≥ 50 years, in addition to the abovementioned factors [OR = 2.38, P = 0.0355 for CKD stages 4-5; OR = 3.49, P = 0.0094 for family history of intracranial aneurysm or subarachnoid hemorrhage], female sex (OR = 4.51, P = 0.0005), and hypertension (OR = 5.89, P = 0.0012) were also associated with intracranial aneurysm. CONCLUSION: Kidney dysfunction and family history of intracranial aneurysm or subarachnoid hemorrhage are risk factors for early-onset intracranial aneurysm. Patients aged < 50 years with a family history of intracranial aneurysm or subarachnoid hemorrhage or with CKD stages 4-5 may be at an increased risk of early-onset intracranial aneurysm.

Comparative outcomes of hemodialysis patients facing pre-Omicron and Omicron COVID-19 epidemics.

INTRODUCTION: This study elucidates factors affecting the severity and mortality in pre-Omicron and Omicron strains of SARS-CoV-2 and vaccination impact. METHODS: This single-center retrospective observational study included 1598 hospitalized COVID-19 patients. Patients were grouped into "pre-Omicron" and "Omicron" periods. The endpoint was severe COVID-19 (oxygen saturation [SpO2 ] < 94%). Logistic regression examined associations between clinical factors, including hemodialysis (HD), and the endpoint. RESULTS: The HD patient mortality rate dropped from 16% pre-Omicron to 4% during the Omicron epidemic. HD was significantly associated with the study endpoint in both epidemics. Unvaccinated patients had a greater risk of reaching the study endpoint among patients receiving HD. CONCLUSION: These findings suggest that the Omicron variant, alongside vaccination and healthcare innovations, led to improved prognoses for HD patients with COVID-19. However, HD patients remain at a greater risk for severe COVID-19. Increased vaccination rates and optimized healthcare resources can improve this vulnerable population's prognoses.

Immediate drop of urine osmolality upon tolvaptan initiation predicts impact on renal prognosis in patients with ADPKD.

BACKGROUND AND HYPOTHESIS: Tolvaptan, a vasopressin V2 receptor antagonist, is used for treating autosomal dominant polycystic kidney disease (ADPKD). We focused on changes in urinary osmolality (U-Osm) after tolvaptan initiation to determine whether they were associated with the therapeutic response to tolvaptan. METHODS: This was a single-centre, prospective, observational cohort study. Seventy-two patients with ADPKD who received tolvaptan were recruited. We analysed the relationship between changes in U-Osm and annual estimated glomerular filtration rate (eGFR) in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The mean value of U-Osm immediately before tolvaptan initiation was 351.8 ± 142.2 mosm/kg H2O, which decreased to 97.6 ± 23.8 mosm/kg H2O in the evening. The decrease in U-Osm was maintained in the outpatient clinic 1 month later. However, the values of U-Osm showed higher variability (160.2 ± 83.8 mosm/kg H2O) than did those in the first evening of tolvaptan administration. Multivariate analysis revealed that the baseline eGFR, baseline urinary protein, and U-Osm change in the evening of the day of admission (initial U-Osm drop) were significantly correlated with the subsequent annual change in eGFR. CONCLUSIONS: U-Osm can be measured easily and rapidly, and U-Osm change within a short time after tolvaptan initiation may be a useful index for the renal prognosis in actual clinical practice.

A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib.

The number of patients with diabetic nephropathy is increasing worldwide and it is important to understand the underlying pathological mechanisms of the disease. In early stage diabetic nephropathy, the hyperglycemic environment leads to vascular endothelial cell damage, resulting in overexpression of vascular endothelial growth factor (VEGF) in podocytes and renal pathology of glomerular hypertrophy, glomerular basement membrane thickening, and mesangial hyperplasia. In diabetic nephropathy, renal thrombotic microangiopathy (TMA) develops and the nephropathy progressively worsens in some cases of severe glomerular podocyte damage. Further, receptor tyrosine kinase inhibitors (RTKIs) may suppress VEGF secretion via VEGF receptor-2 tyrosine kinase inhibition in podocytes, which results in renal TMA and rapid deterioration of diabetic nephropathy. Osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR)-TKI, is approved as a first-line treatment agent for metastatic or locally advanced EGFR mutation-positive non-small cell lung cancer. We encountered a case of a patient with diabetic nephropathy with lung adenocarcinoma treated with osimertinib, whose condition deteriorated from early nephropathy to end-stage renal disease in approximately 4 months. The patient had early diabetic nephropathy, but the use of a RTKI suppressed VEGF expression in podocytes, resulting in the induction of renal TMA and the development of rapidly progressive diabetic nephropathy.

Association between Diabetic Peripheral Neuropathy as Measured Using a Point-of-Care Sural Nerve Conduction Device and Urinary Albumin Excretion in Patients with Type 2 Diabetes.

BACKGROUND: It is not well known whether diabetic peripheral neuropathy diagnosed using a non-invasive point-of-care nerve conduction device called DPN-Check® is associated with diabetic nephropathy. Thus, we aimed to evaluate the association of diabetic peripheral neuropathy with urinary albumin excretion in patients with type 2 diabetes using DPN-Check®. METHODS: This retrospective observational study included 323 Japanese patients with type 2 diabetes. The urinary albumin-to-creatinine ratio in a spot urine sample was defined as urinary albumin excretion. Multiple linear regression analysis was used to determine the association of DPN-Check®-determined diabetic peripheral neuropathy with urinary albumin excretion. RESULTS: Patients with DPN-Check®-determined diabetic peripheral neuropathy had significantly higher urinary albumin excretion than those without, while there was no difference in urinary albumin excretion between patients with and without diabetic peripheral neuropathy determined by simplified diagnostic criteria. In the multivariate model, the DPN-Check® determined that diabetic peripheral neuropathy was significantly associated with urinary albumin excretion even after adjustment for covariates (standardized ß, 0.123; p = 0.012). CONCLUSIONS: Our study found a significant association between diabetic peripheral neuropathy diagnosed using DPN-Check® and urinary albumin excretion in patients with type 2 diabetes.

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.

Impact of kidney function and kidney volume on intracranial aneurysms in patients with autosomal dominant polycystic kidney disease.

Presently, only personal or family history of intracranial aneurysm/subarachnoid hemorrhage (IA/SAH) has been established as a risk factor for IA in autosomal dominant polycystic kidney disease (ADPKD). This study aimed to verify the association between kidney function/volume and IAs in patients with ADPKD. This study included 519 patients with ADPKD. At baseline IA screening, the median age and estimated glomerular filtration rate were 44 years and 54.5 mL/min/1.73 m2, respectively. Family IA/SAH history was confirmed in 18.1% of the patients, and 54.3% of the patients had hypertension. The IA point prevalence was 12.5%. During clinical follow up of 3104 patient-years, de novo IA was detected in 29 patients (0.93% patient-years). The IA period prevalence was 18.1% (median age, 60 years). Multivariable logistic regression demonstrated that total kidney volume (TKV) ≥ 1000 mL (odds ratio [OR] = 2.81), height-adjusted TKV ≥ 500 mL (OR = 2.81), Mayo imaging classification Class 1D-1E (OR = 2.52), and chronic kidney disease stages 3-5 (OR = 2.31) were significantly associated with IA formation. IAs in patients with ADPKD may be associated not only with general risk factors for IAs but also with declining kidney function and increased KV. Kidney disease progression may contribute to effective IA screening and treatment planning in patients with ADPKD.

Germline Mutations for Kidney Volume in ADPKD.

Introduction: Valid prediction models or predictors of disease progression in children and young patients with autosomal dominant polycystic kidney disease (ADPKD) are lacking. Although total kidney volume (TKV) and Mayo imaging classification are generally used to predict disease progression in patients with ADPKD, it remains unclear whether germline mutation types are associated with these factors. We therefore investigated the association between mutation type and TKV and Mayo imaging classification among patients with ADPKD. Methods: A total of 129 patients with ADPKD who underwent genetic analyses were enrolled in the study. The associations between the severity of PKD (TKV ≥ 1000 ml and Mayo classes 1C-1E) and the PKD1 mutation types (nonsense mutation, frameshift or splicing mutation, and substitution) were evaluated. Results: Among the mutation types, only PKD1 splicing/frameshift mutation had significant associations with TKV ≥ 1000 ml in sex-adjusted and multivariable logistic analyses. Similarly, only the PKD1 splicing/frameshift mutation was significantly associated with Mayo 1C-1E in sex-adjusted and multivariable logistic analyses. PKD1 nonsense mutation, PKD1 substitution, or PKD1 mutation position had no significant association with TKV ≥ 1000 ml or Mayo 1C-1E. Conclusion: Kidney cyst severity differs according to the mutation types in PKD1. Patients with PKD1 splicing mutations or PKD1 frameshift mutations are associated with TKV ≥ 1000 ml or Mayo 1C-1E. Detailed assessment of mutation types may be useful for predicting renal prognosis in patients with ADPKD and may especially contribute to the care of a high-risk group of children with ADPKD.

Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease.

BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients. METHODS: This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The initial eGFR change was - 4.6 ± 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased. CONCLUSIONS: The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan.

Urinary Aquaporin 2 as a Potential Indicator Predicting Tolvaptan Response in Patients With ADPKD.

INTRODUCTION: Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) because it inhibits binding of the antidiuretic hormone vasopressin to the vasopressin V2 receptor (V2R), which suppresses the insertion of preformed water channel aquaporin 2 (AQP2) molecules in the luminal membrane of the collecting duct cells. METHODS: This single-center, prospective observational cohort study investigated whether decreased AQP2 elimination in urine affects the renal prognosis of patients who received tolvaptan. We selected 92 patients with ADPKD who were administered tolvaptan in our hospital. We evaluated correlations between changes in urinary AQP2 (U-AQP2) and clinical parameters and the annual change in total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) as renal prognostic factors using univariable and multivariable multiple regression analyses. RESULTS: The observation period was 2.4 ± 1.5 years. U-AQP2 per milligram of urinary creatinine (U-AQP2/Cr) decreased from 67.8 ± 50.6 to 20.7 ± 15.1 fmol/mg urinary creatinine after 1 month of tolvaptan treatment. This initial change in U-AQP2/Cr was correlated with high baseline U-AQP2/Cr, low baseline eGFR, and a large initial change in eGFR (baseline to 1 month). The initial change in U-AQP2/Cr (baseline to 1 month) was strongly correlated with the annual change in TKV and eGFR in multivariable analysis. CONCLUSION: Initial decrease in U-AQP2/Cr in the first month of treatment reflects the pharmacologic effect of tolvaptan and could be an indicator of renal prognosis during tolvaptan treatment.

The Importance of Phosphate Control in Chronic Kidney Disease.

A series of problems including osteopathy, abnormal serum data, and vascular calcification associated with chronic kidney disease (CKD) are now collectively called CKD-mineral bone disease (CKD-MBD). The pathophysiology of CKD-MBD is becoming clear with the emerging of αKlotho, originally identified as a progeria-causing protein, and bone-derived phosphaturic fibroblast growth factor 23 (FGF23) as associated factors. Meanwhile, compared with calcium and parathyroid hormone, which have long been linked with CKD-MBD, phosphate is now attracting more attention because of its association with complications and outcomes. Incidentally, as the pivotal roles of FGF23 and αKlotho in phosphate metabolism have been unveiled, how phosphate metabolism and hyperphosphatemia are involved in CKD-MBD and how they can be clinically treated have become of great interest. Thus, the aim of this review is reconsider CKD-MBD from the viewpoint of phosphorus, its involvement in the pathophysiology, causing complications, therapeutic approach based on the clinical evidence, and clarifying the importance of phosphorus management.

Predicting liver cyst severity by mutations in patients with autosomal-dominant polycystic kidney disease.

BACKGROUND: Most patients with autosomal-dominant polycystic kidney disease (ADPKD) develop liver cysts and polycystic liver disease as they age. To date, no simple clinical indicator has been confirmed to predict polycystic liver disease exacerbation. Furthermore, the effect of the type and location of mutation on disease progression of polycystic liver disease remains unclear. Here, we aimed to establish a simple liver cyst indicator for clinical practice and investigate whether gene mutations determined liver phenotype in patients with autosomal-dominant polycystic kidney disease. METHODS: In total, 129 patients with ADPKD were enrolled and liver cyst indicators were assessed based on mutation type (truncating mutation: nonsense, frameshift, and splicing mutation; non-truncating mutation: substitution) and mutation position. Liver cyst severity was determined using Gigot and Drenth classifications, based on their number, maximum diameter, and area ratio with the liver. RESULTS: We observed an overall prevalence of 62.8% for polycystic liver disease. Patients with PKD1 nonsense mutations, a type of PKD1 truncating mutation, exhibited more severe liver disease phenotypes than those without the mutation. We identified maximum diameter as a potential liver cyst indicator. Moreover, a subgroup analysis that included a PKD1 nonsense mutation cohort revealed that genetic mutations located closer to the 5' end of PKD1 were associated with a maximum diameter index value ≥ 6 cm. CONCLUSION: PKD1 nonsense mutations were associated with liver cyst severity, which along with maximum diameter index as a simple clinical indicator for liver cysts, may improve the treatment of polycystic liver disease associated with ADPKD.

Impact of visceral fat area in patients with chronic kidney disease.

Longitudinal studies evaluating the association between visceral fat area (VFA) and kidney function decline in patients with chronic kidney disease (CKD) are limited, and little is known about VFA interactions contributing to the kidney prognosis (e.g. interactions between VFA ≥ 100 cm2 and age, sex, and CKD category). In this study, we stratified patients with CKD according to VFA category, as well as age, sex, CKD category, hyperglycemia, and diabetes mellitus, and determined the ability of obesity-related indicators (body mass index, waist circumference, subcutaneous fat area, visceral-to-subcutaneous fat ratio) to predict the renal prognosis. Kidney outcomes (≥ 50% estimated glomerular filtration rate decline or end-stage kidney disease) were examined in 200 patients with CKD (median follow-up, 12.3 years). On multivariable Cox analysis, an increase in VFA (10-cm2 increase) was significantly associated with kidney outcomes in the entire cohort, and VFA was significantly associated with kidney disease progression even in the VFA < 100 cm2 sub-cohort. Interestingly, the hazard ratio (HR) was higher for VFA (10-cm2 increase) than for the VFA ≥ 100 cm2 sub-cohort (HR 1.33 vs. 1.07). Overall, VFA was found to be the most versatile obesity-related indicator associated with kidney disease progression. VFA was associated with the primary outcome in the sub-cohorts of CKD stages 1-2, hyperglycemia, and diabetes mellitus. A high VFA was a significant kidney prognostic factor in the entire CKD cohort, with greater significance in patients with VFA < 100 cm2 than in patients with VFA ≥ 100 cm2. Our results may provide new insights into strategies for treating CKD.

Dose-Dependent Effect of Tolvaptan on Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease.

This is the first report to describe dose dependency in the effects of tolvaptan treatment for autosomal dominant polycystic kidney disease.The weight-adjusted average daily dose of tolvaptan was found to be a factor that significantly affected the change in eGFR.If a patient shows tolerance, increasing the tolvaptan dose to the maximum should be considered.

Maximum Carotid Intima-Media Thickness in Association with Renal Outcomes.

AIM: We aimed to examine the association between the maximum intima-media thickness of the carotid artery (Max IMT) and renal prognosis, considering their potential interaction with age. METHODS: Survival analyses were performed in 112 patients with chronic kidney disease (CKD), to assess renal prognosis, with the endpoint defined as a ≥ 30% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease. RESULTS: During a median follow-up of 12.5 years, 44 participants reached the study endpoint. The major determinant of Max IMT was the maximum IMT of the internal carotid artery (Max ICA-IMT), which was the distribution ratio of 50.0% of Max IMT. Kaplan-Meier analyses showed that Max IMT ≥ 1.5 mm was significantly associated with renal prognosis when age and eGFR were matched. On multivariate Cox regression analysis, Max IMT was significantly associated with the renal outcomes and had a significant interaction with the age categories (≥ 65 years or ＜65 years) (P=0.0153 for interaction). A 1-mm increase in Max IMT was significantly associated with disease progression in the sub-cohort ＜65 years age-category, but not in the ≥ 65 years age-category; similarly the hazard ratio (HR) in the ＜65 years age-category was higher than in the ≥ 65 years age-category (HR: 2.52 vs. 0.95). Comparable results were obtained for Max ICA-IMT, Max bulb-IMT, but not for Max common carotid artery-IMT. CONCLUSIONS: A higher Max IMT was a significant renal prognosis factor in patients with CKD aged ＜65 years. Our results may provide new insights into treating CKD.

Sex Differences in Time-Series Changes in Pseudo-R2 Values Regarding Hyperuricemia in Relation to the Kidney Prognosis.

Studies on sex differences in time-series changes in pseudo-R2 values regarding hyperuricemia (HU) in relation to the kidney prognosis among patients with chronic kidney disease (CKD) are scant. The kidney prognosis was evaluated in 200 patients with CKD (median follow-up, 12.3 years). Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R2 values. We used four definitions of HU according to serum uric acid (SUA) levels (HU6, SUA ≥ 6.0 mg/dL; HU7, SUA ≥ 7.0 mg/dL; HU8, SUA ≥ 8.0 mg/dL) and antihyperuricemic agent use to calculate the mean and percentage of the change in pseudo-R2 values from the 6th year until the end of the study (6Y-End Mean and 6Y-End Change, respectively). The multivariable Cox regression analysis showed that HU7 was significantly associated with kidney outcomes. When stratified by sex, the 6Y-End Mean was clearly higher in women than in men for all HU definitions, with the highest value (0.1755) obtained for HU7 in women. The pseudo-R2 values for HU6 in women showed an increasing pattern, with a 6Y-End Change of 11.4%/year. Thus, it may be clinically meaningful to consider sex differences in the time-series pseudo-R2 values regarding HU and kidney outcomes.

Visceral to subcutaneous fat ratio as an indicator of a ≥30% eGFR decline in chronic kidney disease.

Whether the visceral-to-subcutaneous fat ratio (V/S ratio) is associated with renal prognosis in patients with chronic kidney disease (CKD) remains unclear. Furthermore, little is known about the effect of sex and the absolute amount of visceral fat accumulation such as visceral fat area (VFA) ≥100 cm2 on the V/S ratio in relation to renal prognosis. In this study, 200 patients with CKD were evaluated for renal prognosis. Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R2 values. The mean and percent change of the pseudo-R2 values from the 6th year to the 10th year (6Y-10Y Mean and 6Y-10Y Change, respectively) were calculated for determining the cut-off points for the medium-term renal prognosis. Multivariate Cox regression analysis revealed that the V/S ratio was significantly associated with renal outcomes and that the VFA category (VFA ≥ 100 cm2) had significant interactions with the V/S ratio regarding renal prognosis. The hazard ratio (HR) of the V/S ratio was higher in the sub-cohort of VFA < 100 cm2 than in the sub-cohort of VFA ≥ 100 cm2 (HR: 6.42 vs. 1.00). Regarding sex differences, a strong association was noted between the V/S ratio and renal prognosis in women but not in men (HR: 2.40 vs. 1.10). On the other hand, 6Y-10Y Mean of the pseudo-R2 values indicated differences in the cut-off points of the V/S ratio between men and women (V/S ratio: 0.75 vs. 0.5). Our findings indicate that it may be clinically meaningful to consider the differences in sex and the amount of VFA ≥100 cm2 for the V/S ratio in relation to renal outcomes in patients with CKD. The 6Y-10Y Mean of the pseudo-R2 values contributed to determining the cut-off points of the V/S ratio according to the sex difference.

Time series changes in pseudo-R2 values regarding maximum glomerular diameter and the Oxford MEST-C score in patients with IgA nephropathy: A long-term follow-up study.

There is no effectual pathological factor to predict the long-term renal prognosis of IgA nephropathy. Glomerular hypertrophy plays a crucial role in kidney disease outcomes in both experimental models and humans. This study aimed to 1) confirm the long-term prognostic significance of a maximal glomerular diameter (Max GD) ≥ 242.3 µm, 2) test a renal prognosis prediction model adding Max GD ≥ 242.3 µm to the Oxford classification (MEST-C), and 3) examine the time series changes in the long-term renal prognosis of patients with IgA nephropathy. The study included 43 patients diagnosed with IgA nephropathy from 1993 to 1998 at Kameda General Hospital. Renal prognosis with the endpoint of a 50% reduction in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease requiring dialysis was examined using logistic regression analysis, Cox regression analysis, and the Kaplan-Meier method. Pathological evaluation was performed using MEST-C and Max GD, and the validity of the prediction model was evaluated. Patients with Max GD ≥ 242.3 µm had significantly poor renal prognosis with multivariate Cox analysis (P = 0.0293). The results of the Kaplan-Meier analysis showed that kidney survival rates in the high-Max GD group were significantly lower than those in the low-Max GD group (log rank, P = 0.0043), which was confirmed in propensity score-matched models (log rank, P = 0.0426). Adding Max GD ≥ 242.3 µm to MEST-C improved diagnostic power of the renal prognosis prediction model by renal pathology tissue examination (R2: 3.3 to 14.5%, AICc: 71.8 to 68.0, C statistic: 0.657 to 0.772). We confirm that glomerular hypertrophy is useful as a long-term renal prognostic factor.