The latest medical research on Nephrology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about nephrology gathered by our medical AI research bot.

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Effects of caloric restriction and aerobic exercise on circulating cell-free mitochondrial DNA in patients with moderate-to-severe chronic kidney disease.

American Journal of

Circulating cell-free mitochondrial DNA (ccf-mtDNA) may induce systemic inflammation, a common condition chronic kidney disease (CKD), by acting as...

Temporal Trends of Dietary Risk Factors after a Diagnosis of Kidney Stones.

Clinical Journal of the American

Diet is an important contributor to kidney stone formation, but there are limited data regarding long-term changes in dietary factors after a diagn...

Use of Race in Kidney Research and Medicine.

Clinical Journal of the American

Black Americans and other racially and ethnically minoritized individuals are disproportionately burdened by higher morbidity and mortality from ki...

Noninvasive Diagnosis of PLA2R-Associated Membranous Nephropathy: A Validation Study.

Clinical Journal of the American

Kidney biopsy is the current gold standard to diagnose membranous nephropathy. Approximately 70%-80% of patients with primary membranous nephropathy have circulating anti-phospholipase A2 receptor antibodies. We previously demonstrated that in proteinuric patients with preserved eGFR and absence of associated conditions (e.g., autoimmunity, malignancy, infection, drugs, and paraproteinemia), a positive anti-phospholipase A2 receptor antibody test by ELISA and immunofluorescence assay confirms the diagnosis of membranous nephropathy noninvasively. These data have not been externally validated.

The clinical and pathologic characteristics of patients with a positive anti-phospholipase A2 receptor antibody test at the Mayo Clinic, the University Hospital Vall D'Hebron (Barcelona), and the Columbia University Medical Center (New York) were retrospectively reviewed. Biopsy findings and presence or absence of a potential associated condition were assessed.

From a total of 276 patients with positive anti-phospholipase A2 receptor serology, previously reported patients (n=33), kidney transplant recipients (n=9), pediatric patients (n=2), and patients without kidney biopsy (n=69) were excluded. Among the 163 remaining patients, associated conditions were identified in 47 patients, and 15 patients had diabetes mellitus. All 101 patients of the final cohort had a primary diagnosis of membranous nephropathy on kidney biopsy. In the 79 patients with eGFR≥60 ml/min per 1.73 m2, none of the biopsy findings altered diagnosis or management. Among the 22 patients with decreased eGFR, additional findings included superimposed acute interstitial nephritis (n=1).

In patients with preserved eGFR and absence of associated conditions or diabetes, a positive anti-phospholipase A2 receptor test by either ELISA >20 RU/ml or a positive immunofluorescence assay confirms the diagnosis of membranous nephropathy, precluding the requirement for a kidney biopsy.

Association of Polypharmacy with Kidney Disease Progression in Adults with CKD.

Clinical Journal of the American

Polypharmacy is common in patients with CKD and reportedly associated with adverse outcomes. However, its effect on kidney outcomes among patients with CKD has not been adequately elucidated. Hence, this investigation was aimed at exploring the association between polypharmacy and kidney failure requiring KRT.

We retrospectively examined 1117 participants (median age, 66 years; 56% male; median eGFR, 48 ml/min per 1.73 m2) enrolled in the Fukushima CKD Cohort Study to investigate the association between the number of prescribed medications and adverse outcomes such as kidney failure, all-cause mortality, and cardiovascular events in Japanese patients with nondialysis-dependent CKD. Polypharmacy and hyperpolypharmacy were defined as the regular use of 5-9 and ≥10 medications per day, respectively.

The median number of medications was eight; the prevalence of polypharmacy and hyperpolypharmacy was each 38%. During the observation period (median, 4.8 years), 120 developed kidney failure, 153 developed cardiovascular events, and 109 died. Compared with the use of fewer than five medications, adjusted hazard ratios (95% confidence intervals) associated with polypharmacy and hyperpolypharmacy were 2.28 (1.00 to 5.21) and 2.83 (1.21 to 6.66) for kidney failure, 1.60 (0.85 to 3.04) and 3.02 (1.59 to 5.74) for cardiovascular events, and 1.25 (0.62 to 2.53) and 2.80 (1.41 to 5.54) for all-cause mortality.

The use of a high number of medications was associated with a high risk of kidney failure, cardiovascular events, and all-cause mortality in Japanese patients with nondialysis-dependent CKD under nephrology care.

Klotho overexpression protects against renal aging along with suppressions of transforming growth factor-β1 signaling pathways.

American Journal of

Klotho is an anti-aging protein reported to suppress transforming growth factor (TGF)-b1 signaling. Aging kidneys are characterized by interstitial...

Bladder infection with uropathogenic Escherichia coli increases the excitability of afferent neurons.

American Journal of

Urinary tract infections (UTIs) cause bladder hyperactivity and pelvic pain, but the underlying causes of these symptoms remain unknown. We investi...

Functional Reserve of the Kidney.

Clinical Journal of the American

The exploration of the normal limits of physiological responses and how these responses are lost when the kidney is injured are rarely used in clin...

Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease.

Clinical Journal of the American

Biomarkers for non-invasive assessment of histopathology and prognosis are needed in patients with kidney disease.

Using a proteomics assay, we measured a multi-marker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semi-quantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of kidney replacement therapy) and death.

After multivariable adjustment and correction for multiple testing, 57 proteins were associated with different histopathologic lesions. The top performing markers positively associated with acute tubular injury and interstitial fibrosis and tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and immunoglobulin domain-containing protein 2 (VSIG2), respectively. 30 proteins were significantly associated with kidney disease progression and 35 with death. The top performing markers for kidney disease progression were placental growth factor (HR per doubling 5.4, 95% CI 3.4 to 8.7) and BMP and Activin Membrane Bound Inhibitor (HR 3.0, 95% CI 2.1 to 4.2); the top performing markers for death were TRAIL-receptor-2 (HR 2.9, 95% CI 2.0 to 4.0) and CUB Domain Containing Protein-1 (HR 2.4, 95% CI 1.8 to 3.3).

We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases.

Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis.

Clinical Journal of the American

Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy.

Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation.

In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation (P=0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse.

The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events.

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3.

Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation.

Clinical Journal of the American

Age and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis. To overcome these confounding factors, alterations in skeletal muscle were analyzed in highly selected patients on long-term hemodialysis undergoing kidney transplantation.

In total, 22 patients on long-term hemodialysis scheduled for kidney transplantation with few comorbidities, but with a long-term uremic milieu exposure, and 22 age, sex, and physical activity level frequency-matched control participants were recruited. We compared biochemical, functional, and molecular characteristics of the skeletal muscle using maximal voluntary force and endurance of the quadriceps, 6-minute walking test, and muscle biopsy of vastus lateralis. For statistical analysis, mean comparison and multiple regression tests were used.

In patients on long-term hemodialysis, muscle endurance was lower, whereas maximal voluntary force was not significantly different. We observed a transition from type I (oxidative) to type II (glycolytic) muscle fibers, and an alteration of mitochondrial structure (swelling) without changes in DNA content, genome replication (peroxisome proliferator activator receptor γ coactivator-1α and mitochondrial transcription factor A), regulation of fusion (mitofusin and optic atrophy 1), or fission (dynamin-related protein 1). Notably, there were autophagosome structures containing glycogen along with mitochondrial debris, with a higher expression of light chain 3 (LC3) protein, indicating phagophore formation. This was associated with a greater conversion of LC3-I to LC3-II and the expression of Gabaralp1 and Bnip3l genes involved in mitophagy.

In this highly selected long-term hemodialysis population, a low oxidative phenotype could be defined by a poor endurance, a fiber-type switch, and an alteration of mitochondria structure, without evidence of sarcopenia. This phenotype could be related to uremia through the activation of autophagy/mitophagy.

NCT02794142 and NCT02040363.

Airflow Limitation, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients.

Clinical Journal of the American

Many kidney transplant recipients suffer from fatigue and poor health-related quality of life. Airflow limitation may be an underappreciated comorbidity among kidney transplant recipients, which could contribute to fatigue and lower health-related quality of life in this population. In this study, we compared the prevalence of airflow limitation between kidney transplant recipients and healthy controls and investigated associations of airflow limitation with fatigue and health-related quality of life in kidney transplant recipients.

Data from the ongoing TransplantLines Biobank and Cohort study were used. Airflow limitation was defined as forced exhaled volume in 1 second less than the fifth percentile of the general population. Fatigue and health-related quality of life were assessed using checklist individual strength 20 revised (CIS20-R) and Short Form-36 (SF-36) questionnaires.

A total of 539 kidney transplant recipients (58% men; mean age 56±13 years) and 244 healthy controls (45% men; mean age 57±10 years) were included. Prevalence of airflow limitation was higher in kidney transplant recipients than in healthy controls (133 [25%] versus 25 [10%]). In multinomial regression models, airflow limitation was independently associated with fatigue severity (odds ratio moderate fatigue, 1.68; 95% confidence interval, 0.92 to 3.09 and odds ratio severe fatigue, 2.51; 95% confidence interval, 1.39 to 4.55; P=0.007) and lower physical health-related quality of life (-0.11 SDs; 95% confidence interval, -0.19 to -0.02; P=0.01) in kidney transplant recipients. In exploratory mediation analyses, fatigue accounted for 79% of the association of airflow limitation with physical health-related quality of life.

Airflow limitation is common among kidney transplant recipients. Its occurrence is associated with more than two times higher risk of severe fatigue, and it is associated with lower physical health-related quality of life. Mediation analyses suggest that airflow limitation causes fatigue, which in turn, decreases physical health-related quality of life.

TransplantLines: The Transplantation Biobank, NCT03272841 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN06600521.mp3.