American Journal of Nephrology最新文献

Introduction: Rituximab has proven effective and safe in pediatric and adult minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients with frequently relapsing nephrotic syndrome. However, its efficacy diminishes in several patients who experience nephrotic syndrome relapsing in short durations or failing to achieve remission. We aimed to explore the efficacy and safety of obinutuzumab, a novel anti-CD20 antibody, in these patients.

Methods: A retrospective case series study at our center included 11 adult MCD or FSGS patients who presented with nephrotic syndrome characterized by short-duration relapses or lack of remission after multitarget therapy, including rituximab. Primary outcomes included the first relapse-free time, relapse rate during follow-up, and the use of immunosuppressants after obinutuzumab. All adverse events were recorded.

Results: Eleven adult patients (median age 26.0 years, 81.9% males) received an average obinutuzumab dose of 2.0 (1.0, 2.0) g during a median follow-up period of 17.0 (12.0, 22.0) months. The first relapse-free time was 12.1 (10.8, 18.9) months. Two patients with FSGS experienced relapses, while the remaining maintained remission by the end of follow-up. Six patients (54.5%) achieved cessation of corticosteroids and immunosuppressants within 3 months after obinutuzumab. Adverse events were mostly mild.

Conclusion: Obinutuzumab may be an efficient and safe option for inducing remission in adult MCD and FSGS patients who presented with nephrotic syndrome relapsing in short durations or failed to achieve remission after multitarget therapy, including rituximab. It was effective in maintaining remission in MCD patients, while its efficacy in maintaining remission in FSGS patients remained uncertain.

Introduction: There are conflicting reports about the effect or rapamycin on the kidneys. Rapamycin is known to promote phosphaturia that may be associated to renal injury.

Methods: Detailed histopathological studies were performed on the kidneys of rats with normal (control) and reduced (Nx) renal mass that were treated with rapamycin (1.3 mg/kg for 22 days) or placebo. The effect of rapamycin was also evaluated in control and Nx rats fed different amounts of phosphorus: 0.6% P (NP), 1.2% P (HP), and 0.2% P (LP). Quantitative scores of kidney lesions were obtained for interstitial nephritis (IN), tubular damage (TD), and nephrocalcinosis (NC).

Results: When compared with placebo, rapamycin administration to Nx rats resulted in significant increases in IN (4.17 ± 0.74 vs. 1.51 ± 0.53%) and TD (14.45 ± 1.51 vs. 8.61 ± 1.83%). Rapamycin also increased NC both in control (0.86 ± 0.23 vs. 0.14 ± 0.06%) and Nx (0.86 ± 0.32 vs. 0.15 ± 0.14%) rats. In control rats receiving rapamycin, feeding HP aggravated IN (3.25 ± 0.48%), TD (22.47 ± 4.56%), and NC (3.66 ± 0.75%), while feeding LP prevented development of any renal lesions. In Nx rats treated with rapamycin, HP intake also increased IN (8.95 ± 1.94%), TD (26.86 ± 3.95%), and NC (2.77 ± 0.60%), whereas feeding LP reduced all lesions to lower levels than in rats fed NP. Rapamycin treatment increased fractional excretion of P (FEP), and an excellent correlation between scores for renal lesions and FEP was found.

Conclusion: Rapamycin has deleterious effects on kidney pathology causing lesions that are located mainly at tubular and tubulointerstitial level. Rapamycin-induced kidney damage is more evident in rats that already have decreased renal function and seems to be related to the phosphaturic effect of the drug. Dietary P restriction prevents kidney damage in rats treated with rapamycin.

Introduction: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles. The genetic types of HPS are associated with a spectrum of multisystemic clinical manifestations. Phenotypic features of HPS type 1 (HPS-1) or HPS-4, which are associated with defects in biogenesis of lysosome-related organelles complex-3 (BLOC-3), are generally more severe than those of HPS-3, HPS-5, or HPS-6, which are associated with defects in BLOC-2. A paucity of information is available about renal impairment in HPS. The objective of this study is to expand the understanding of kidney disease in HPS.

Methods: Medical records and clinical data of patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2020 were retrospectively reviewed. For patients with more than one visit, the most recent renal function and urinalysis tests were analyzed. Estimated glomerular filtration rate (eGFR) was calculated using standard equations (i.e., Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease). Kidney tissue sections from 5 patients with HPS-1 and 1 patient with HPS-6 were examined.

Results: Records from 205 adults and 52 children with HPS were reviewed. Calculated eGFR of adult patients with different HPS types differed significantly, and calculated eGFR of pediatric and adult patients with BLOC-3 disorders was significantly lower than that of patients with BLOC-2 disorders. Linear regression analysis showed that renal function progressively decreases with age in patients with BLOC-3 or BLOC-2 disorders, but the rate of decline was more rapid in patients with BLOC-3 disorders compared to patients with BLOC-2 disorders. In adult patients with HPS-1, glucosuria was found in 4%, proteinuria in 12%, hematuria in 15%, high levels of urinary β2MG in 24%, and elevated urinary albumin to creatinine ratios in 9%. Histological examination of kidney tissue showed accumulation of intracellular deposits of ceroid lipofuscin in proximal renal tubular epithelial cells in patients with HPS-1. There was no evidence of fibrosis, and glomeruli, distal renal tubular epithelial cells, and interstitial regions appeared histologically normal.

Conclusion: Mild impairment of renal function is a feature of HPS. Kidneys of patients with HPS-1 contain proximal renal tubular intracellular deposits and no histologic evidence of fibrosis. Consistent with other manifestations of HPS, the phenotype of renal impairment is relatively more pronounced in patients with BLOC-3 disorders than in patients with BLOC-2 disorders. Strategies to avoid nephrotoxicity or renal tubular injury and to protect renal function should be considered for patients with HPS irrespective of age.

Introduction: The field of living kidney donation is profoundly gendered contributing to a predominance of women, mothers, and wives as living kidney donors (LKDs). Individual factors have traditionally been emphasized, and there is a limited appreciation of relational, community, and sociocultural influences in decision-making. We aimed to comprehensively capture existing evidence to examine the relative importance of these factors.

Methods: This was a systematic review of existing literature that has explored the motivation of different genders to become LKDs. Of the 3,188 records screened, 16 studies from 13 counties were included. Data were synthesized thematically using the Social-Ecological Model lens.

Results: At the individual level, themes related to intrinsic motivation; thoughtful deliberation; and attitudes, fears, and beliefs; however, evidence demonstrating differences between men and women was minimal. Greater variation between genders emerged along the relational (coercion from family/network, relationship with the intended recipient, self-sacrifice within the family unit, and stability/acceptance within family); community (economic value and geographic proximity to recipient); and sociocultural (gendered societal roles, social norms and beliefs, social privilege, and legislation and policy) dimensions. The relative importance of each factor varied by context; cultural components were inferred in each study, and economic considerations seemed to transcend the gender divide.

Conclusions: A complex interplay of factors at relational, community, and sociocultural levels influences gender roles, relations, and norms and manifests as gender disparities in living kidney donation. Our findings suggest that to address gender disparities in living donation, dismantling of deep-rooted systemic contributors to gender inequities is needed.

Introduction: Non-alcoholic fatty liver disease (NAFLD) has emerged as a potential indicator for cardio-metabolic risk. However, clinical implications of NAFLD in patients with chronic kidney disease (CKD) are still elusive. We investigated to explore the association between NAFLD and adverse clinical outcomes among patients with CKD.

Methods: In this national population-based retrospective cohort study, we analyzed 816,857 individuals who underwent National Health Insurance Service health examinations and had an estimated glomerular filtration rate of 15-59 mL/min/1.73 m2. The main predictor was the fatty liver index (FLI), a surrogate marker for NAFLD. The primary outcome was a composite cardiovascular or kidney events, which were examined combined or separately.

Results: During a median follow-up of 7.7 (IQR, 6.4-9.6) years, the composite outcome events occurred in 74,266 (9.1%) individuals. Among these, there were 55,525 (6.8%) cardiovascular events and 22,961 (2.8%) kidney events, respectively. Compared to FLI of <30, the hazard ratio (HRs; 95% confidence intervals [CIs]) for the composite outcome were 1.16 (1.14-1.18) and 1.30 (1.26-1.33) for the FLIs of 30-59 and ≥60, respectively. The corresponding HRs for cardiovascular events were 1.21 (95% CI, 1.18-1.23) and 1.36 (95% CI, 1.31-1.40), respectively. Furthermore, FLIs of 30-59 and ≥60 were associated with an 11% (HR, 1.11; 95% CI, 1.07-1.15) and 24% (HR, 1.24; 95% CI, 1.17-1.30) increased risk of kidney events, respectively.

Conclusions: NAFLD was associated with higher risk of adverse clinical outcomes in individuals with CKD. These findings suggest that NAFLD, as assessed by the FLI, can serve as a predictor of cardiovascular and kidney events in CKD population.

Introduction: The definition of CKD is broad, which neglects the heterogeneity of risk across primary renal diseases.

Methods: The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD is an ongoing UK, prospective multicenter cohort study of 2,996 adults with an eGFR of 15-59 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73 m2 with a urine albumin-to-creatinine ratio (uACR) >30 mg/mmol. Outcomes and predictive performance of eGFR and uACR were subcategorized by ERA-EDTA primary renal diagnosis (PRD) codes.

Results: 2,638 participants were included, with baseline median eGFR of 33.5 mL/min/1.73 m2 and uACR 29.8 mg/mmol. Over a median 49.2 months follow-up, 630 (23.9%) experienced kidney failure (KF), and 352 (13.3%) died before KF, the median eGFR slope was -1.97 mL/min/1.73 m2/year. There were significant differences in risk across the PRD, persisting after adjustment for age, sex, baseline eGFR, and modifiable risk factors (blood pressure, HbA1c, and renin-angiotensin-aldosterone system inhibitors). Diabetic kidney disease (DKD), glomerulonephritis, and familial/hereditary nephropathy were associated with the greatest risk, while tubulointerstitial disease and vasculitis carried a low risk of KF. eGFR had good predictive accuracy across all PRD. However, the addition of uACR showed variable benefit, depending on the PRD. The largest benefit was seen in vasculitis, renal vascular, and DKD groups, but uACR added no predictive value to the familial/hereditary group.

Conclusion: Significant differences in the risk of kidney-related outcomes occurred across the various primary renal diagnoses persisting after adjustment for age, sex, baseline eGFR, and modifiable risk factors. Albuminuria's discriminatory ability as a biomarker of progression varies by diagnosis. CKD care should, therefore, take a personalized approach that always considers the primary renal diagnosis.

Introduction: Mycophenolate mofetil (MMF) is widely used off-label in patients with immunoglobulin A nephropathy (IgAN), although the literature does not consistently agree on its efficacy and safety.

Methods: We systematically searched PubMed, Embase, CENTRAL, CNKI, VIP, Wanfang Data, and SinoMed from their inception to August 2023. We included randomized controlled trials that enrolled patients of IgAN who received MMF treatment and compared effects with placebo or as an add-on therapy to usual care. Literature screening, risk of bias assessment, and data extraction were independently conducted in duplicate. Fixed-effects or random-effects meta-analyses were performed for pooling data where eligible. The primary outcomes were the composite kidney outcomes of major adverse kidney events (MAKDE) defined as doubling of serum creatinine, end-stage renal disease (ESRD), or death from a kidney disease-related or cardiovascular cause.

Results: Of 13 studies identified, 918 participants (463 [50.4%] treated with MMF) with IgAN were included in the analysis. MMF treatment in IgAN was associated with decreasing the occurrence of MAKDE (relative risk [RR], 0.32; 95% confidence interval [CI], 0.13-0.77), reducing proteinuria (RR, 1.41; 95% CI, 1.22-1.64), and lessening the probability of doubling blood creatinine (RR, 0.32, 95% CI, 0.14-0.72). No significant differences were detected in the incidence of ESRD (RR, 0.87, 95% CI, 0.38-2.03), or progression of chronic kidney disease (RR, 1.01; 95% CI, 0.22-4.57). Patients receiving MMF had a higher risk of infection (RR, 2.20; 95% CI, 1.21-4.00).

Conclusion: MMF administration in IgAN indicates promising in decreasing the occurrence of MAKDE, reducing proteinuria level, and lessening the probability of doubling blood creatinine, but also comes with the risk of infection. These findings tend to be introduced to non-Caucasian population. The long-term favorable effects that MMF improved kidney outcomes still need further cross-regional and cross-ethnical verification.

Introduction: The role of dietary sodium intake in the risk of chronic kidney disease progression remains controversial. This study aimed to evaluate the association of urinary sodium excretion and progression of IgA nephropathy.

Methods: We assessed 596 patients with IgA nephropathy, and urinary sodium excretion was measured at the time of kidney biopsy. Cox proportional hazards models and restricted cubic splines were used to assess the association between urinary sodium excretion and kidney disease progression events, defined as 50% eGFR decline or development of kidney failure.

Results: After a mean follow-up of 58.9 months, a total of 75 (12.6%) participants of IgA nephropathy reached composite kidney disease progression events. The risk of kidney disease progression events was higher in patients with higher urinary sodium excretion. After adjustment for traditional risk factors, higher levels of ln-transformed urinary sodium excretion was associated with the kidney disease progression events in patients with IgA nephropathy (HR: 2.1; 95% CI: 1.4-3.2). In reference to the first tertile of urinary sodium excretion, hazard ratios were 1.9 (95% CI: 1.0-3.4) for the second tertile and 2.1 (95% CI: 1.1-3.9) for the third tertile.

Conclusion: Higher levels of urinary sodium excretion were associated with kidney disease progression events in IgA nephropathy independent of clinical and biopsy characteristics.

Introduction: Moderate vitamin A levels during pregnancy are strongly related to normal embryonic development in both animal models and population studies. Abnormal development of urinary tract system is linked to either an excess or a shortage of vitamin A. The relationships among maternal vitamin A deficiency prior to conception, moderate vitamin A supplementation during pregnancy, and abnormal urinary system development in offspring are unclear.

Methods: By creating preconception and preconception + pregnancy vitamin A insufficiency mouse models, we investigated whether moderate vitamin A treatment during pregnancy may reduce the prevalence of CAKUT and increase distant vitamin A levels in offspring, as well as any potential pathways involved.

Results: We effectively established a prepregnancy vitamin A-deficient mouse model by providing a particular diet with or without vitamin A for 4 weeks. The offspring of the hypovitaminosis A model group presented a greater proportion of neonatal urinary tract developmental malformations. Abnormalities in ureteral bud emergence and key molecules during renal development, such as p-Plcγ and Ret, may be the primary causes of offspring development of CAKUT as a result of mothers' hypovitaminosis A. Normal vitamin A diets, on the other hand, may help mitigate the teratogenic consequences of prepregnancy hypovitaminosis A, as well as defects produced by ureteral budding and major molecular changes.

Conclusion: In contrast, the administration of normal vitamin A feeds during pregnancy may ameliorate the teratogenic effects of prepregnancy hypovitaminosis A to a certain extent and may also ameliorate the abnormalities associated with ureteral budding and key molecular changes.

Introduction: Worsening renal function poses a significant health risk to elderly individuals. This study aimed to construct a simple risk prediction model for new-onset chronic kidney disease (CKD) among elderly populations.

Methods: In this retrospective cohort study, 5,416 elderly residents (aged ≥65 years) who underwent physical examinations as part of the National Basic Public Health Service project at least twice between January 2017 and July 2021 were included. The endpoint was new-onset CKD, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 during the follow-up period. Predictors of new-onset CKD were selected using multivariable Cox regression and a stepwise approach. A risk prediction model based on the selected predictors was constructed and evaluated using the concordance index (C-index) and area under curve (AUC). External validation was conducted to verify the model's performance.

Results: During the median follow-up period of 2.3 years, the incident of new-onset CKD was 20.1% (n = 1,088). Age, female gender, diabetes, elevated triglyceride levels, and baseline eGFR were selected as predictors. The model demonstrated good predictive performance across the cohort, with a C-index of 0.802. The AUCs for 2-year, 3-year, and 4-year predictions were 0.831, 0.829, and 0.839, respectively. External validation confirmed the model's efficacy, with a 2-year AUC of 0.735.

Conclusion: This study developed a simple yet effective risk prediction model for new-onset CKD among elderly populations. The model facilitates prompt identification of elderly individuals at risk of renal function decline in primary care, enabling timely interventions.