Podocyte density as a predictor of long-term kidney outcome in obesity-related glomerulopathy.

Glomerulomegaly and focal segmental glomerulosclerosis are histopathological hallmarks of obesity-related glomerulopathy (ORG). Podocyte injury and subsequent depletion are regarded as key processes in the development of these glomerular lesions in patients with ORG, but their impact on long-term kidney outcome is undetermined. Here, we correlated clinicopathological findings and podocyte depletion retrospectively in patients with ORG. Relative (podocyte density) and absolute (podocyte number per glomerulus) measures of podocyte depletion were estimated using model-based stereology in 46 patients with ORG. The combined endpoint of kidney outcomes was defined as a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure. Patients with lower podocyte density were predominantly male and had larger body surface area, greater proteinuria, fewer non-sclerotic glomeruli, larger glomeruli and higher single-nephron eGFR. During a median follow-up of 4.1 years, 18 (39%) patients reached endpoint. Kidney survival in patients with lower podocyte density was significantly worse than in patients with higher podocyte density. However, there was no difference in kidney survival between patient groups based on podocyte number per glomerulus. Cox hazard analysis showed that podocyte density, but not podocyte number per glomerulus, was associated with the kidney outcomes after adjustment for clinicopathological confounders. Thus, our study demonstrates that a relative depletion of podocytes better predicts long-term kidney outcomes than does absolute depletion of podocytes. Hence, the findings implicate mismatch between glomerular enlargement and podocyte number as a crucial determinant of disease progression in ORG.

Long-Term Outcomes, Including Fetal and Neonatal Prognosis, of Renal Oligohydramnios: A Retrospective Study over 22 Years.

OBJECTIVE: To assess the long-term outcome of renal oligohydramnios and risk factors for fetal, neonatal, and postneonatal death. STUDY DESIGN: This retrospective cohort study included fetuses with prenatally detected renal oligohydramnios between 2002 and 2023. Patients who were lost to follow-up were excluded. Fetal, neonatal, and long-term outcomes were evaluated, and their risk factors were analyzed. RESULTS: Of 131 fetuses with renal oligohydramnios, 46 (35%) underwent a termination of pregnancy, 11 (8%) had an intrauterine fetal death, 26 (20%) had a neonatal death, nine (7%) had a postneonatal death, and 39 (30%) survived. Logistic regression analyses showed that an earlier gestational age at onset (OR 1.16, 95% CI 1.01-1.37) was significantly associated with intrauterine fetal death; anhydramnios (OR 12.7, 95% CI 1.52-106.7) was significantly associated with neonatal death as a prenatal factor. Although neonatal survival rates for bilateral renal agenesis, bilateral multicystic dysplastic kidney (MCDK), and unilateral MCDK with contralateral renal agenesis were lower than for other kidney diseases, 1 case of bilateral renal agenesis and two of bilateral MCDK survived with fetal intervention. Kaplan-Meier overall survival rates were 57%, 55%, and 51% for 1, 3, and 5 years, respectively. In the Cox proportional hazards model, birth weight <2000 g (hazard ratio 7.33, 95% CI 1.48-36.1) and gastrointestinal comorbidity (hazard ratio 4.37, 95% CI 1.03-18.5) were significant risk factors for postneonatal death. CONCLUSION: Long-term survival following renal oligohydramnios is a feasible goal and its appropriate risk assessment is important.

Chronic Tonsillitis and IgA Nephropathy: Findings From a Nationwide Japanese Cohort Study.

RATIONALE & OBJECTIVE: Little is known regarding the association between chronic tonsillitis and the onset of IgA nephropathy (IgAN). In the present study, we examined the potential relationship between chronic tonsillitis and a subsequent risk of developing IgAN. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 4,311,393 individuals without a history of IgAN identified between January 2005 and May 2022 within a Japanese nationwide epidemiological database, the JMDC Claims Database, representing health claims to over 60 insurers. EXPOSURE: Comorbid chronic tonsillitis based on diagnosis codes. OUTCOME: IgAN occurrence. ANALYTICAL APPROACH: Cause-specific Cox proportional hazards analysis adjusting for potential confounding factors was employed to estimate hazard ratios (HRs). RESULTS: Comorbid chronic tonsillitis was identified in 12,842 individuals, constituting 0.3% of the cohort. The cohort had a median age of 44 years (IQR, 36-53), and males accounted for 57.9%, with a follow-up of 1,089 days (IQR, 532-1,797), during which 2,653 cases of IgAN developed. Cumulative incidence curve showed a higher cumulative incidence of IgAN in individuals with chronic tonsillitis compared with their counterparts without this condition. Multivariable cause-specific analysis further demonstrated that individuals with chronic tonsillitis had an elevated risk of developing IgAN, with HR of 2.72 (95% CI, 1.79-4.14). LIMITATIONS: Potential residual confounders, and lack of consideration for ethnic distinctions. CONCLUSIONS: Using a large-scale epidemiological dataset, these findings suggest a relationship between chronic tonsillitis and an elevated risk of IgAN development in the general Japanese population. PLAIN-LANGUAGE SUMMARY: IgA nephropathy (IgAN), the most prevalent form of primary glomerulonephritis worldwide, is associated with unfavorable long-term kidney survival and life expectancy. Despite the substantial implications, the early detection of IgAN still remains challenging due to its commonly asymptomatic clinical presentation. Consequently, the exploration of risk factors assumes a critical research priority. Prior studies have reported the potential role of tonsilitis in the pathogenesis of IgAN. In this study, we assessed whether chronic tonsillitis was associated with the subsequent development of IgAN using a nationwide epidemiological dataset incorporating over 4,000,000 individuals. Within this large-scale cohort, our findings revealed an association between a history of tonsillitis and a greater risk of developing IgAN. These findings should heighten awareness of the potential susceptibility of people with chronic tonsilitis to IgAN.

Dose-dependent association between estimated glomerular filtration rate and the subsequent risk of depression: An analysis of a nationwide epidemiological dataset.

BACKGROUND: Although the risk of depression is well-known in the patients with kidney dysfunction, especially at the late stages, little is known about the exact point at which the decline in estimated glomerular filtration rate (eGFR) begins to significantly increase the risk of depression. In the present study, we analysed a nationwide epidemiological dataset to investigate the dose-dependent association between baseline eGFR and a future risk of developing depression in a general population. METHODS: We retrospectively analysed 1,518,885 individuals (male: 46.3%) without a history of depression identified between April 2014 and November 2022 within a nationwide epidemiological database, provided by DeSC Healthcare (Tokyo, Japan). We investigated the association of eGFR with the incidence of depression using Cox regression analyses and also conducted cubic spline analysis to investigate the dose-dependent association between eGFR and depression. RESULTS: In the mean follow-up of 1218 ± 693 days, 45,878 cases (3.0% for total participants, 2.6% for men and 3.3% for women) of depression were recorded. The risk of depression increased with the eGFR decline as well as the presence of proteinuria. Multivariable Cox regression analysis showed the hazard ratio (95% CI) of depression in each kidney function category (eGFR ≥90, 60-89, 45-59, 30-44, 15-29, and < 15 mL/min/1.73 m2) was 1.14 (1.11-1.17), 1 (reference), 1.11 (1.08-1.14), 1.51 (1.43-1.59), 1.77 (1.57-1.99) and 1.77 (1.26-2.50), respectively. In the cubic spline analysis, the risk of depression continued to increase monotonically as the eGFR declined when the eGFR fell below approximately 65 mL/min/1.73 m2. CONCLUSIONS: Our analysis using a large-scale epidemiological dataset presented the dose-dependent association between eGFR decline and the risk of depression, which highlights the importance of incorporating mental health assessments into the routine care of patients with kidney dysfunction, regardless of the stage of their disease.

Proton Pump Inhibitors and Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Hemodialysis Patients: Results from the Japan Dialysis Outcomes and Practice Patterns Study.

INTRODUCTION: Hyporesponsiveness to erythropoiesis stimulating agents (ESAs) is important problem in dialysis patients. While proton pump inhibitors (PPIs) may inhibit iron absorption, few studies have examined associations between PPIs and ESA-resistant anemia in hemodialysis patients. This study examined the associations between PPIs and ESA-resistant anemia in hemodialysis patients. METHODS: The present study was a cross-sectional study using repeated 4-month observations, up to eight observations/patient, from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS). The primary outcome was erythropoietin resistance index (ERI). ESA dose, hemoglobin, proportion of erythropoietin-resistant anemia, transferrin saturation (TSAT), and ferritin were also examined. Linear or risk-difference regression models were used with generalized estimating equations to account for repeated measurements. RESULTS: Of 1,644 patients, 867 patients had PPI prescriptions (52.7%). Patients prescribed PPI had higher ERI, higher ESA dose, and lower TSAT levels. Multivariable analysis for 12,048 four-month observations showed significantly greater ERI in PPI users (adjusted difference 0.95 IU/week/kg/[g/dL] [95% CI: 0.40-1.50]). Significant differences were also found in ESA dose (336 IU/week [95% CI: 70-602]) and the prevalence of erythropoietin-resistant anemia (3.9% [2.0-5.8%]) even after adjusted for TSAT and ferritin. Among possible mediators between the association of PPIs and anemia, TSAT was significantly different between PPI users and non-users (adjusted difference, -0.82% [95% CI: -1.56 to -0.07]). CONCLUSIONS: This study showed the associations between PPI and ERI, ESA dose, and TSAT in hemodialysis patients; physicians should consider anemia's associations with PPIs in hemodialysis patients.

Significance of eGFR and proteinuria for cardiovascular disease in individuals beyond 85 years.

BACKGROUND: There are limited data on how advancing age influences prediction of CVD risk based on the estimated glomerular filtration rate (eGFR) and proteinuria, especially in older adults, including those aged ≥ 85 years. This study aimed to clarify the association of eGFR and proteinuria with CVD outcomes and the impact of age on this association. METHODS: The distribution of eGFR and urine protein in Japan was assessed retrospectively using real-world administrative claims and health checkup data collected between April 2014 and November 2022. We investigated the associations of these two parameters with the incidence of CVD, with an emphasis on the impact of aging. RESULTS: We assessed 1 829 020 individuals for distribution of eGFR and proteinuria; after excluding those with known CVD, their association with CVD risk was examined in 1 040 101 individuals aged ≥ 40 years. The prevalence of impaired kidney function (eGFR <60 mL/min/1.73 m2) increased with age, being 0.7%, 9.2%, 21.9%, 40.2%, and 60.2% at the ages of 18-39, 40-64, 65-74, 75-84, and ≥ 85 years (P for trend < 0.001); similarly, the proportion with positive proteinuria increased with age, being 2.7%, 4.3%, 5.6%, 9.2%, and 15.8%, respectively (P for trend < 0.001). Both eGFR and urine protein were identified to be independent risk factors for CVD. Hazard ratios for CVD increased significantly when eGFR was <45 mL/min/1.73 m2 at the ages of 40-64, 65-74, and 75-84 and <30 mL/min/1.73 m2 at ≥ 85 years, while proteinuria remained significantly associated with a high CVD risk regardless of age. These findings were consistent even when analyzed separately by sex. CONCLUSIONS: This study identified eGFR and urine dipstick proteinuria to be independent risk factors for CVD, even among individuals aged ≥ 85 years. However, the contribution of eGFR to the CVD risk was attenuated by aging, whereas proteinuria remained less affected by advancing age.

Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

Long-term effects of denosumab on bone mineral density and turnover markers in patients undergoing hemodialysis.

INTRODUCTION: Denosumab, a fully human anti-RANKL monoclonal antibody, is a widely used osteoporosis treatment that is increasingly being used in patients undergoing dialysis; however, its long-term efficacy and safety in these patients remain unknown. MATERIALS AND METHODS: This observational study comprised individuals aged ≥ 20 years undergoing hemodialysis and receiving denosumab. After denosumab administration, we analyzed the long-term changes in bone mineral density (BMD) and levels of bone turnover markers (BTMs) and calcium. RESULTS: The study included 45 patients who have been receiving denosumab for a median duration of 3.8 (interquartile range, 2.5-6.7) years. Tartrate-resistant acid phosphatase 5b (TRACP-5b) levels decreased from a median of 595 (434-778) mU/dL at baseline to 200 (141-430) mU/dL after 6 months of denosumab administration (P < 0.001) and remained low thereafter. Similarly, bone-specific alkaline phosphatase (BAP) levels decreased from a median of 18.2 (15.9-25.8) µg/L at baseline to 12.4 (9.9-15.6) µg/L after 6 months (P < 0.001) and remained low thereafter. Meanwhile, BMD, as assessed with dual energy X-ray absorptiometry and measured at the distal 1/3 of the radius, did not decrease (0.465 ± 0.112 g/cm2 at baseline vs. 0.464 ± 0.112 g/cm2 after administration; P = 0.616). Regarding hypocalcemia, corrected calcium levels reached were the lowest at 7 days after administration and normalized within 30 days. CONCLUSION: The study showed long-term suppression of TRACP-5b and BAP levels and sustaining BMD after denosumab administration over an extended period in patients undergoing hemodialysis.

Association Between Parathyroid Hormone-Related Peptide Levels and Mortality in Patients With Malignancy.

OBJECTIVE: Hypercalcemia of malignancy is a risk factor for mortality in patients with malignancies. Although the parathyroid hormone-related protein (PTHrP) secreted by tumor cells induces hypercalcemia, the association between serum PTHrP levels and mortality remains unclear. This study aimed to investigate the association between serum PTHrP levels and mortality in patients with malignancies. METHODS: We included patients with hypercalcemia (>10 mg/dL) and elevated PTHrP levels (>1.1 pmol/L) and analyzed mortality (overall survival after cancer diagnosis, PTHrP measurement, and 5-year survival rate). Moreover, using Cox proportional hazard model analysis, we investigated the impact of PTHrP levels on survival prognosis, assessing whether this effect varied depending on calcium concentration. RESULTS: We analyzed the data of 183 patients. The median PTHrP level, corrected calcium level, and age were 5.5 (3.0-10.6) pmol/L, 12.5 (11.5-13.4) mg/dl, and 70 (61-76) years, respectively. PTHrP was significantly and linearly associated with serum calcium levels (correlation coefficient, 0.06; 95% CI: 0.039-0.081, t: 5.69; P < .001). The group with the highest PTHrP levels had significantly worse survival rates than the group with the lowest PTHrP levels (hazard ratio: 1.68, 95% CI 1.03-2.77, P = .038). CONCLUSION: This study showed an association between PTHrP and mortality in patients with malignancy after adjusting for serum calcium levels.

The relation between proteinuria and the severity of COVID-19.

BACKGROUND: The association between proteinuria, which is also an indicator of chronic kidney disease (CKD), and coronavirus disease 2019 (COVID-19) severity is unclear. METHODS: We selected 342 hospitalized patients with COVID-19 diagnosed via polymerase chain reaction testing between February 2020 and October 2022 and who had at least one urinalysis 14-365 days before admission. RESULTS: Proteinuria before admission was associated neither with oxygen administration nor developing pneumonia in multivariate analysis (odds ratio [OR] 1.03; 95% confidence interval (CI) 0.44-2.40, p = 0.95 and OR 1.01; 95% CI 0.47-2.17, p = 0.98, respectively). Proteinuria on admission was associated both with oxygen administration and developing pneumonia in multivariate analysis (OR 3.29; 95% CI 1.37-7.88, p < 0.01 and OR 3.81; 95% CI 1.68-8.62, p < 0.01, respectively). The percentage of patients with proteinuria on admission was significantly higher than those before admission (37.4% vs. 17.8%; p < 0.01). In the subgroup analysis, proteinuria on admission among patients with eGFR ≥ 60 mL/min/1.73 m2 was associated with both oxygen administration and developing pneumonia (OR 4.86; 95% CI 1.22-19.38, p = 0.03, OR 3.65; 95% CI 1.06-12.58, p = 0.04, respectively). In contrast, proteinuria on admission among patients with eGFR < 60 mL/min/1.73 m2 was associated with developing pneumonia (OR 6.45; 95%CI 1.78-23.35, p = 0.01), not with oxygen administration (OR 3.28; 95% CI 0.92-11.72, p = 0.07). CONCLUSIONS: Although underlying proteinuria before admission was not associated with COVID-19 severity, proteinuria on admission was associated with oxygen demand and developing pneumonia.

Association between serum magnesium levels and cognitive function in patients undergoing hemodialysis.

BACKGROUND: The relationship between chronic kidney disease-mineral and bone disorder (CKD-MBD) and cognitive function remains largely unknown. This cross-sectional study aimed to explore the association between CKD-MBD and cognitive function in patients on hemodialysis. METHODS: Hemodialysis patients aged ≥ 65 years without diagnosed dementia were included. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). CKD-MBD markers, serum magnesium, intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), fibroblast growth factor (FGF)-23, and soluble α-klotho were measured. RESULTS: Overall, 390 patients with a median age of 74 (interquartile range, 70-80) years, mean serum magnesium level of 2.4 ± 0.3 mg/dL, and median MoCA and MMSE scores of 25 (22-26) and 28 (26-29), respectively, were analyzed. MoCA and MMSE scores were significantly higher (preserved cognitive function) in the high-magnesium group than in the low-magnesium group according to the unadjusted linear regression analysis (ß coefficient [95% confidence interval (CI)] 1.05 [0.19, 1.92], P = 0.017 for MoCA; 1.2 [0.46, 1.94], P = 0.002 for MMSE) and adjusted multivariate analysis with risk factors for dementia (ß coefficient [95% CI] 1.12 [0.22, 2.02], P = 0.015 for MoCA; 0.92 [0.19, 1.65], P = 0.014 for MMSE). CONCLUSIONS: Higher serum magnesium levels might be associated with preserved cognitive function in hemodialysis patients. Conversely, significant associations were not observed between cognitive function and intact PTH, 25-OHD, FGF-23, or soluble α-klotho levels.

Estimating the prevalence of chronic kidney disease in the older population using health screening data in Japan.

BACKGROUND: In aging societies, the prevalence of chronic kidney disease (CKD) is expected to increase but may be underestimated because many asymptomatic patients remain undiagnosed. This study aimed to estimate the CKD prevalence among the general older population in Japan. METHODS: This cross-sectional study used health screening data from the Japan Health Insurance Association collected between April 2014 and March 2023. Data from older people aged 65-90 years who underwent renal function screening for estimated glomerular filtration rate (eGFR) and urine protein tests were analyzed. CKD was defined as eGFR < 60 mL/min/1.73 m2 or proteinuria ≥ 1 + . Inverse probability weighting was used to account for the selection bias. The variables used for weighting were age, sex, insurance status, and the number of previous screenings. RESULTS: Among 2.98 million older individuals, 588,809 (19.7%) had undergone screening (median [IQR] age, 69.9 [67.9-76.2] years, 337,862 women [57.4%]). Regarding the weighted CKD prevalence, 25.3% of the individuals aged 65-90 years had CKD; 11.8% of those aged 65-75 years and 34.6% of those aged 75 years and over showed an increase in prevalence with age. Among the patients with CKD, over half exhibited mild renal dysfunction without proteinuria. Hypertension and diabetes were common comorbidities in older patients with CKD. CONCLUSIONS: This cross-sectional study revealed that the weighted prevalence of CKD in the older population aged 65-90 years was high (one in four individuals), indicating that it increases with age. Further studies are required to examine the clinical significance of these findings.

Association between the serum zinc level and nutritional status represented by the geriatric nutritional Rrisk index.

BACKGROUND: Although it is widely known that patients with chronic kidney disease (CKD) can develop zinc deficiency, in our previous analysis, the estimated glomerular filtration rate (eGFR) was not independently associated with the serum zinc level. Thus, a post hoc analysis was conducted to investigate the involvement of nutritional status. METHODS: A total of 655 subjects not on dialysis (402 males; mean age, 57 ± 18 years) who underwent serum zinc level measurements at Jikei University Hospital between April 2018 and March 2019 were selected using the Standardized Structured Medical Information eXchange2 (SS-MIX2) system. In addition, anthropometric data and the Geriatric Nutritional Risk Index (GNRI) representing nutritional status were obtained, and the relationship between the serum zinc level and nutritional status was investigated by multiple regression analysis. RESULTS: The serum albumin level and the GNRI were lower in the zinc-deficiency group, and both were positively associated with the serum zinc level (rho = 0.44, P < 0.01 and rho = 0.44, P < 0.01, respectively). On multiple regression analysis, the GNRI (t = 3.09, P < 0.01) and serum albumin level (t = 4.75, P < 0.01) were independently associated with the serum zinc level. Although a higher eGFR was associated with a higher serum zinc level, this association disappeared on multivariate analysis. CONCLUSION: In this post hoc analysis, the GNRI, as well as the serum albumin level, were correlated with the serum zinc level, indicating that nutritional status is an important determinant of the zinc level. Further investigations are needed to clarify the effects of nutritional status and kidney function on zinc deficiency.

Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.

BACKGROUND: Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. METHODS: Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4 years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. RESULTS: The femoral neck's BMD decreased from 0.836 g/cm2 (0.702-0.952) to 0.764 g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4 years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833 g/cm2 (0.736-0.965) to 0.824 g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [ß-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [ß-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CONCLUSION: CBPB administration may be associated with BMD maintenance.

Analysis of the impact of obesity on the prognosis of IgA nephropathy according to renal function and sex.

BACKGROUND: Few studies have observed the direct effect of obesity on renal prognoses in immunoglobulin A nephropathy (IgAN) or separately evaluated its effects according to sex. We aimed to evaluate the direct and indirect effects of obesity on the renal outcomes of IgAN and observe these effects separately according to renal function and sex. METHODS: We extracted patients with body mass index (BMI) descriptions from a multicenter retrospective cohort analysis in Japan, and excluded those with < 30 days of follow-up, diabetes mellitus, and steroid treatment. Patients were divided into normal (n = 720; 18.5 ≤ BMI < 25) and obese (n = 212; BMI ≥ 25) groups, which were then compared. The endpoints were a 1.5-fold increase in serum creatinine levels and the initiation of renal replacement therapy. RESULTS: The obese group was older, included more males, and was more likely have hypertension, dyslipidemia, proteinuria, tubular atrophy, and lower renal function than the normal group. Patients with an eGFR < 60 mL/min/1.73 m2 had well-matched characteristics between the groups; however, hypertension, low high-density lipoprotein cholesterol, and hypertriglyceridemia were more common in the obese group. Obesity contributed to tubular atrophy, even when adjusted for renal function. In addition, it contributed to proteinuria only in females. However, obesity itself was not a significant prognostic factor. CONCLUSIONS: Although no independent effect on renal prognosis was observed during the study period, the obese group had more risk factors for IgAN progression and obesity contributed to tubular atrophy and female proteinuria. Our results suggest that separately analyzing the prognostic effect of obesity according to sex is important.

Estimating baseline creatinine levels based on the kidney parenchymal volume.

BACKGROUND: Acute kidney injury (AKI) diagnosis often lacks a baseline serum creatinine (Cr) value. Our study aimed to create a regression equation linking kidney morphology to function in kidney donors and chronic kidney disease patients. We also sought to estimate baseline Cr in minimal change disease (MCD) patients, a common AKI-predisposing condition. METHODS: We analyzed 119 participants (mean age 60 years, 50% male, 40% donors) with CT scans, dividing them into derivation and validation groups. An equation based on kidney parenchymal volume (PV) was developed in the derivation group and validated in the validation group. We estimated baseline Cr in 43 MCD patients (mean age 45 years, 61% male) using the PV-based equation and compared with their 6 month post-MCD onset Cr values. RESULTS: In the derivation group, the equation for the estimated glomerular filtration rate (eGFR) was: eGFR (mL/min/1.73m2) = 0.375 × PV (cm3) + (- 0.395) × age (years) + (- 2.93) × male sex + (- 13.3) × hypertension + (- 14.0) × diabetes + (- 0.210) × height (cm) + 82.0 (intercept). In the validation group, the eGFR and estimated Cr values correlated well with the measured values (r = 0.46, p = 0.01; r = 0.51, p = 0.004, respectively). In the MCD group, the baseline Cr values were significantly correlated with the estimated baseline Cr values (r = 0.52, p < 0.001), effectively diagnosing AKI (kappa = 0.76, p < 0.001). CONCLUSIONS: The PV-based regression equation established in this study holds promise for estimating baseline Cr values and diagnosing AKI in patients with MCD. Further validation in diverse AKI populations is warranted.

Effect of tonsillectomy combined with steroid pulse therapy upon IgA nephropathy depending on proteinuria status at diagnosis: a nationwide multicenter cohort study in Japan.

BACKGROUND: The effects of tonsillectomy combined with steroid pulse (TSP) therapy for IgA nephropathy (IgAN) are little known. Therefore, we examined the effects of TSP therapy on the kidney outcomes of IgAN in a large, nationwide cohort study in Japan. METHODS: Between 2002 and 2004, 632 IgAN patients with ≥ 0.5 g/day proteinuria at diagnosis were divided into three groups with mild (0.50-0.99 g/day; n = 264), moderate (1.00-1.99 g/day, n = 216), or severe (≥ 2.00 g/day; n = 153). Decline in kidney function and urinary remission were compared among the three groups after TSP therapy, corticosteroid (ST) therapy, or conservative therapy during a mean follow-up of 6.2 ± 3.3 years. 10.6% and 5.9% of patients in the ST and conservative therapy group underwent tonsillectomy. RESULTS: The rate of urinary remission at the final observation was significantly higher in the TSP therapy group than in the ST or conservative therapy groups (mild proteinuria: 64%, 43%, and 41%; moderate proteinuria: 51%, 45%, and 28%; severe proteinuria: 48%, 30%, and 22%, respectively). In contrast, the rate of a 50% increase in serum creatinine was lower in groups TSP therapy, than ST or conservative therapy (mild proteinuria: 2.1%, 10.1% and 16.7%; moderate proteinuria: 4.8%, 8.8% and 27.7%; severe proteinuria: 12.0%, 28.9% and 43.1%, respectively). In multivariate analysis, TSP therapy significantly prevented a 50% increase in serum creatinine levels compared with conservative therapy in groups with moderate and severe proteinuria (hazard ratio, 0.12 and 0.22, respectively). CONCLUSION: TSP significantly increased the rate of proteinuria disappearance and urinary remission in IgAN patients with mild-to-moderate urinary protein levels. It may also reduce the decline in kidney function in patients with moderate-to-severe urinary protein levels.

Upward-directed exit-site of the swan-neck catheter and "Easy-to-disinfect the backside area of exit-site" may prevent PD complications.

BACKGROUND: Upward-directed exit-site has been believed to be the worst for frequent ESI by an old retrospective study using straight catheters. No comparison study of 3 exit-site directions using swan-neck catheter has been performed regarding which direction is the best for our endpoints, Easy-to-see the backside area of exit-site: ESBE, Easy-to-disinfect the backside area of exit-site: EDBE, reduction of both exit-site infection (ESI), symptomatic catheter dislocation and peritonitis. METHODS: We assessed the relationship of exit-site direction with our endpoints in a quantitative cross-sectional, multicentered questionnaire survey. Patients who received either non-surgical catheter implantation or exit-site surgery were excluded. RESULTS: The numbers (percentage) of exit-site directions in included 291 patients were upward 79 (26.0), lateralward 108 (37.5) and downward 105 (36.5). Cochran-Armitage analysis showed a significant step-ladder increase in the prevalence of ESI as the direction changed from upward to lateralward to downward (0.15 ± 0.41, 0.25 ± 0.54, 0.38 ± 0.69 episodes/patient-year, p = 0.03). Multivariable regression analysis revealed the upward exit-site independently associates with both higher frequency of ESBE (OR 5.55, 95% CI 2.23-16.45, p < 0.01) and reduction of prevalence of ESI (OR 0.55, 95%CI 0.27-0.98, p = 0.04). Positive association between the prevalence of symptomatic catheter dislocation and ESI (OR 2.84, 95% CI 1.27-7.82, p = 0.01), and inverse association between EDBE and either prevalence of symptomatic catheter dislocation (OR 0.27, 95% CI 0.11-0.72) or peritonitis (OR 0.48, 95% CI 0.23-0.99) observed. CONCLUSION: Upward-directed swan-neck catheter exit-site may be the best for both ESBE and prevention of ESI. EDBE may reduce catheter dislocation and peritonitis. Symptomatic catheter dislocation may predict ESI.

Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease.

BACKGROUND: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS: This is an analysis of the Japan Chronic Kidney Disease Database Ex　(J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.