Noninvasive and Multiplex Self-Test of Kidney Disease Biomarkers with Graphene-Based Lab-on-a-Chip (G-LOC): Toward Digital Diagnostics in the Hands of Patients.

Chronic kidney disease is one of the major health issues worldwide. However, diagnosis is now highly centralized in large laboratories, resulting in low access to patient monitoring and poor personalized treatments. This work reports the development of a graphene-based lab-on-a-chip (G-LOC) for the digital testing of renal function biomarkers in serum and saliva samples. G-LOC integrates multiple bioelectronic sensors with a microfluidic system that enables multiplex self-testing of urea, potassium, sodium, and chloride. The linearity, limit of detection (LOD), accuracy, and coefficient of variability (CV) were studied. Accuracy values higher than 95.5% and CV lower than 9% were obtained for all of the biomarkers. The analytical performance was compared against three reference lab benchtop analyzers by measuring healthy- and renal-failure-level samples of serum. From receiver operating characteristic (ROC) plots, sensitivities (%) of 99.7, 97.6, 99.1, and 89.0 were obtained for urea, potassium, sodium, and chloride, respectively. Then, the test was evaluated in noninvasive saliva samples and compared against reference methods. Correlation and Bland-Altman plots showed good correlation and agreement of the G-LOC with the reference methods. It is noteworthy that the precision of G-LOC was similar to better than benchtop lab analyzers, with the advantage of being highly portable. Finally, a user testing study was conducted. The analytical performance obtained with untrained volunteers was similar to that obtained with trained chemists. Additionally, based on a user experience survey, G-LOC was found to have very simple usability and would be suitable for at-home diagnostics.

Clinicopathological characteristics and prognosis in patients with monoclonal gammopathy and renal damage in central China: a multicenter retrospective cohort study.

Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies.

Predictive effect of estimated glomerular filtrate rate by creatinine or cystatin C on mortality in patients with coronary artery disease.

BACKGROUND: Renal dysfunction leads to poor prognosis of patients with coronary artery disease (CAD). Current studies have reported the prognosis or mortality of various diseases using different estimated glomerular filtrate rate (eGFR) formulas, while the performance of these equations is unclear in CAD patients. We aim to evaluate the predict effect of creatinine-based eGFR (eGFRcr), cystatin C-based eGFR (eGFRcys), and both creatinine and cystatin C-based eGFR (eGFRcr-cys) in CAD patients. METHODS: A total of 23,178 patients with CAD were included from CIN-II cohort study. The association of eGFRcr, eGFRcys and eGFRcr-cys with cardiovascular and all-cause mortality was detected by Cox regression analysis. The predictive effect of eGFRcr, eGFRcys and eGFRcr-cys on mortality was assessed. RESULTS: During a median follow up of 4.3 years, totally 2051 patients (8.8%) experience all-cause mortality, of which 1427 patients (6.2%) died of cardiovascular disease. For the detection of cardiovascular mortality among CAD patients, eGFRcr-cys had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.730, which was significantly better than eGFRcr (AUC = 0.707, p < 0.001) and eGFRcys (AUC = 0.719, p < 0.001). Similar results were observed in all-cause mortality. Restricted cubic spline showed a U-shaped association between eGFRcr and all outcomes in patients with both reduced and supranormal eGFR levels, while a L-shaped association in eGFRcys and eGFRcr-cys. CONCLUSIONS: Estimated GFR based on both creatinine and cystatin C has highest predictive effect for cardiovascular and all-cause mortality among CAD patients. Meanwhile, supranormal eGFRcr may indicate a higher risk of mortality.

[Consensus on diagnosis and treatment of complement-mediated kidney diseases].

In recent years, the role of complement in various kidney diseases has been gradually elucidated, and drugs targeting complement system have emerged successively, and some of them have been applied in clinical practice. However, there are some problems with complement-targeted therapy. This consensus was initiated by a collaborative group of experts in the diagnosis and treatment of complement-mediated kidney diseases from the medical department of Peking University. Their efforts drew upon domestic and international guidelines/consensuses, as well as the latest literature. The evidence and suggestions on the pathogenesis, diagnosis, complement targeted therapy and vaccine immunization of special pathogenic microorganisms of complement-mediated kidney diseases are briefly described, which aims to provide a reference for the diagnosis and treatment of complement-mediated kidney diseases.

DIAGNOSTIC PERFORMANCE OF BLOOD ANALYTES FOR THE DIAGNOSIS OF RENAL DISEASE IN BLACK-FOOTED FERRETS (MUSTELA NIGRIPES) AT THE PHOENIX ZOO (2001-2020).

Renal disease is an important cause of morbidity and mortality in managed black-footed ferrets (BFF; Mustela nigripes).4,6,12 The objectives of this study were to establish reference intervals for blood analytes of clinically normal BFF (1-2 yr old), summarize the frequency of various renal histopathologic findings in a managed population of BFF, assess the diagnostic performance of blood analytes and urine specific gravity (USG) for the diagnosis of renal disease, and assess if comorbidities or age affects the performance of these analytes in diagnosing renal disease. Reference intervals were established using a cohort (n = 35) of clinically normal, young adult BFF. Postmortem records for all BFF at the Phoenix Zoo between 2001 and 2020 were reviewed, and those with available blood analyte data within 2 wk of death were included (n = 89). Ferrets were placed into one of three groups, based on the organ location of histopathologic abnormalities following necropsy: renal disease as the primary change; those with renal disease and at least one other affected major organ system; or absence of abnormalities in the kidneys. In ferrets with substantial renal changes, the primary diagnosis was amyloidosis (29 of 39; 74.4%). Creatinine, blood urea nitrogen, phosphorus (P), calcium (Ca), Ca:P ratio, USG, globulins, and cholesterol were the best-performing analytes for the diagnosis of renal disease, with an area under the curve of at least 0.90 (95% CI $ 0.80, 1.00). Serum renal markers were within reference intervals in BFF that died without histologic evidence of renal disease. Several blood analytes were significantly affected by age in animals that died of renal disease. This study provides reference intervals for blood analytes in young adult clinically normal BFF and illustrates the clinical utility for the diagnosis of renal disease in this species, particularly creatinine, USG, and P.

Surface-enhanced Raman Spectroscopy in urinalysis of hypertension patients with kidney disease.

Arterial hypertension (AH) is a multifactorial and asymptomatic disease that affects vital organs such as the kidneys and heart. Considering its prevalence and the associated severe health repercussions, hypertension has become a disease of great relevance for public health across the globe. Conventionally, the classification of an individual as hypertensive or non-hypertensive is conducted through ambulatory blood pressure monitoring over a 24-h period. Although this method provides a reliable diagnosis, it has notable limitations, such as additional costs, intolerance experienced by some patients, and interferences derived from physical activities. Moreover, some patients with significant renal impairment may not present proteinuria. Accordingly, alternative methodologies are applied for the classification of individuals as hypertensive or non-hypertensive, such as the detection of metabolites in urine samples through liquid chromatography or mass spectrometry. However, the high cost of these techniques limits their applicability for clinical use. Consequently, an alternative methodology was developed for the detection of molecular patterns in urine collected from hypertension patients. This study generated a direct discrimination model for hypertensive and non-hypertensive individuals through the amplification of Raman signals in urine samples based on gold nanoparticles and supported by chemometric techniques such as partial least squares-discriminant analysis (PLS-DA). Specifically, 162 patient urine samples were used to create a PLS-DA model. These samples included 87 urine samples from patients diagnosed with hypertension and 75 samples from non-hypertensive volunteers. In the AH group, 35 patients were diagnosed with kidney damage and were further classified into a subgroup termed (RAH). The PLS-DA model with 4 latent variables (LV) was used to classify the hypertensive patients with external validation prediction (P) sensitivity of 86.4%, P specificity of 77.8%, and P accuracy of 82.5%. This study demonstrates the ability of surface-enhanced Raman spectroscopy to differentiate between hypertensive and non-hypertensive patients through urine samples, representing a significant advance in the detection and management of AH. Additionally, the same model was then used to discriminate only patients diagnosed with renal damage and controls with a P sensitivity of 100%, P specificity of 77.8%, and P accuracy of 82.5%.

Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.

BACKGROUND: Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs is associated with cardiovascular mortality and kidney disease. This study hypothesizes that urinary prostaglandin E2 (PGE2) and PGE2 metabolite (PGEM) excretions are markers of cardiovascular and kidney health, because they reflect both systemic and kidney-derived PGE2 production. METHODS AND RESULTS: PGE2 and PGEM were measured in spot urine samples from 2291 participants (≥55 years old) of the population-based Rotterdam Study. Urinary PGE2 and PGEM excretions were analyzed using linear regression analyses to identify cross-sectional associations with cardiovascular risk factors and baseline estimated glomerular filtration rate (eGFR). Longitudinal associations with cardiovascular mortality and kidney outcomes (eGFR <60 or <45 mL/min per 1.73 m2 and the composite outcome 40% eGFR loss or kidney failure) were assessed with Cox regression. Urinary PGE2 and PGEM excretions were higher with increasing age, lower eGFR, smoking, diabetes, and albuminuria. A 2-fold higher urinary PGE2 and PGEM excretion was associated with a higher risk of cardiovascular mortality (28 825 patient-years; 160 events; PGE2 hazard ratio [HR], 1.27, [95% CI, 1.06-1.54]; PGEM HR, 1.36 [95% CI, 1.10-1.67]). Higher PGE2 excretions were also associated with a higher risk of incident eGFR <60 mL/min per 1.73 m2 (31 530 person-years; 691 events; HR, 1.13 [95% CI, 1.02-1.25]) with similar HRs for the other kidney outcomes. CONCLUSIONS: Urinary PGE2 and PGEM excretions are novel markers for the presence and progression of cardiovascular and kidney disease. Future studies should address whether these associations are causal and can be targeted to improve cardiovascular and kidney outcomes.

Deep learning applications for kidney histology analysis.

PURPOSE OF REVIEW: Nephropathology is increasingly incorporating computational methods to enhance research and diagnostic accuracy. The widespread adoption of digital pathology, coupled with advancements in deep learning, will likely transform our pathology practices. Here, we discuss basic concepts of deep learning, recent applications in nephropathology, current challenges in implementation and future perspectives. RECENT FINDINGS: Deep learning models have been developed and tested in various areas of nephropathology, for example, predicting kidney disease progression or diagnosing diseases based on imaging and clinical data. Despite their promising potential, challenges remain that hinder a wider adoption, for example, the lack of prospective evidence and testing in real-world scenarios. SUMMARY: Deep learning offers great opportunities to improve quantitative and qualitative kidney histology analysis for research and clinical nephropathology diagnostics. Although exciting approaches already exist, the potential of deep learning in nephropathology is only at its beginning and we can expect much more to come.

El manejo multidisciplinar mejora el diagnóstico genético de las enfermedades renales hereditarias en la era de next generation sequencing (NGS) / Multidisciplinary management improves the genetic diagnosis of hereditary kidney diseases in the next generation sequencing (NGS) era

Antecedentes y objetivo Las enfermedades renales hereditarias (ERH) son una causa frecuente de enfermedad renal crónica, habiéndose incrementado su diagnóstico desde la introducción de la secuenciación masiva (NGS). En 2018 se fundó la Unidad multidisciplinar de Enfermedades Renales Hereditarias de la Región de Murcia basándose en el estudio genético de las ERH mediante panel de genes. El objetivo de este estudio es analizar los resultados obtenidos en los primeros tres años de funcionamiento, así como analizar los factores clínicos que se asocian a la obtención de un diagnóstico genético final. Materiales y métodos Se incluyeron los pacientes estudiados mediante panel de genes de ERH y se compararon las características entre los que obtuvieron un diagnóstico genético final y los que no. Resultados Se estudiaron un total de 360 pacientes, detectándose variantes genéticas en 164 pacientes (45,6%) no relacionados familiarmente. Cuarenta y cinco de estas variantes eran de significado clínico incierto precisando estudio de cosegregación familiar, facilitado por la unidad multidisciplinar. Globalmente, considerando los resultados obtenidos con el panel de NGS realizado en el CBGC y los estudios genómicos ampliados, se consiguió un rendimiento diagnóstico final de ERH del 33,3% (120/360), contando hallazgos incidentales, del 35,6% (128/360). Se estudiaron 223 pacientes con sospecha de síndrome de Alport, confirmándose el diagnóstico en un 28,5% (gen más frecuente COL4A4), los cuales eran con más frecuencia mujeres, y con clara historia familiar compatible. También tenían con más frecuencia microhematuria, aunque 5 pacientes sin microhematuria confirmaron diagnóstico. No hubo diferencias en la edad, proteinuria, función renal, hipoacusia o alteraciones oftalmológicas (AU)

Background and objective Hereditary kidney diseases (HKD) are a frequent cause of chronic kidney disease, and their diagnosis has increased since the introduction of next generation sequencing (NGS). In 2018, the Multidisciplinary Unit for Hereditary Kidney Diseases of the Region of Murcia (UMERH-RM) was founded based on the genetic study of HKD. The objective of this study is to analyze the results obtained in the first 3 years of operation, and to analyze the clinical factors associated to a final genetic diagnosis. Materials and methods All the patients studied with the HKD gene panel were included. The characteristics between those who obtained a final genetic diagnosis and those who did not were compared. Results A total of 360 patients were studied, detecting genetic variants in 164 not related patients (45.6%). 45 of these were variants of uncertain significance requiring a family co-segregation study, which was facilitated by the multidisciplinary unit. Overall, considering the results obtained with the NGS panel and the extended genomic studies, a final diagnostic yield of HRD of 33.3% (120/360) was achieved, and including incidental findings 35.6% (128/360). Two hundred and twenty-three patients with suspected Alport syndrome were studied. Diagnosis was confirmed in 28.5% (COL4A4 most frequent gene), more frequently women with an obvious compatible family history. They also had frequently microhematuria, although 5 patients without microhematuria confirmed the diagnosis. There were no differences in age, proteinuria, renal function, hearing loss, or ophthalmologic abnormalities. The most frequent finding in the renal biopsy was mesangial proliferation. We estimate that 39 patients avoided renal biopsy (AU)

Symptom Science in Kidney Disease.

Physical and emotional symptoms are highly prevalent among patients with kidney disease and are directly linked to impaired health-related quality of life. Symptom science is a field of research aimed at advancing knowledge of the holistic mechanisms driving symptoms, how best to assess symptoms accurately, and developing novel and patient-centered approaches to symptom management. Patients with kidney disease have identified symptom science as a top research priority, and opportunities abound for ongoing patient engagement in symptom-related research efforts and clinical care. This review describes the burden of symptoms experienced by patients with kidney disease, explores the spectrum of patient engagement in symptom care and research, and discusses approaches for symptom assessment and management, taking into consideration the multitude of factors that may contribute to symptoms.

Mind the gap in kidney care: translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Kidney biopsy for the diagnosis and treatment of kidney diseases. Recommendations from the French speaking Society of Nephrology (SFNDT) and French National Authority for Health (HAS) 2022

Kidney Biopsy (KB) is a crucial diagnostic tool in the field of renal diseases and is routinely performed in nephrology departments. A previous survey conducted by the Société Francophone de Néphrologie Dialyse Transplantation (SFNDT) revealed significant disparities in clinical practices, sometimes conflicting with the existing literature and recently published recommendations. In response, the SFNDT wished to promote the development of best practice guidelines, under the auspices of the French National Authority for Health (HAS), to establish a standardized framework for performing kidney biopsies in France.

La biopsie rénale (BR) est un outil diagnostique crucial dans le domaine des maladies rénales et est pratiquée en routine dans les services de néphrologie. Une précédente enquête menée par la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a révélé d'importantes disparités dans les pratiques cliniques, parfois en contradiction avec la littérature existante et les recommandations récemment publiées. En réponse, la SFNDT a souhaité promouvoir l'élaboration de recommandations de bonnes pratiques, sous l'égide de la Haute Autorité de santé (HAS), afin d'établir un cadre standardisé pour la réalisation des biopsies rénales en France.

Selective Partitioned Regression for Accurate Kidney Health Monitoring.

The number of people diagnosed with advanced stages of kidney disease have been rising every year. Early detection and constant monitoring are the only minimally invasive means to prevent severe kidney damage or kidney failure. We propose a cost-effective machine learning-based testing system that can facilitate inexpensive yet accurate kidney health checks. Our proposed framework, which was developed into an iPhone application, uses a camera-based bio-sensor and state-of-the-art classical machine learning and deep learning techniques for predicting the concentration of creatinine in the sample, based on colorimetric change in the test strip. The predicted creatinine concentration is then used to classify the severity of the kidney disease as healthy, intermediate, or critical. In this article, we focus on the effectiveness of machine learning models to translate the colorimetric reaction to kidney health prediction. In this setting, we thoroughly evaluated the effectiveness of our novel proposed models against state-of-the-art classical machine learning and deep learning approaches. Additionally, we executed a number of ablation studies to measure the performance of our model when trained using different meta-parameter choices. Our evaluation results indicate that our selective partitioned regression (SPR) model, using histogram of colors-based features and a histogram gradient boosted trees underlying estimator, exhibits much better overall prediction performance compared to state-of-the-art methods. Our initial study indicates that SPR can be an effective tool for detecting the severity of kidney disease using inexpensive lateral flow assay test strips and a smart phone-based application. Additional work is needed to verify the performance of the model in various settings.

A Rare Case of Page Kidney in a Young Man with Flank Pain.

BACKGROUND: Page kidney is a rare condition in which an external compression of the kidney as a result of a hematoma or mass causes renal ischemia and hypertension. In a patient with flank pain, elevated blood pressure, and recent trauma, this condition should be considered. Since this condition was first described in 1939, more than 100 case reports have surfaced. CASE REPORT: We describe the case of a 26-year-old man who presented to the Emergency Department with flank pain, vomiting, and elevated blood pressure. A computed tomography scan of the abdomen and pelvis confirmed the presence of a perinephric hematoma, and the interventional radiology team was consulted to resolve the Page kidney. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Symptoms seen in Page kidney may be similar to other more common diagnoses encountered in the emergency department. It is important to maintain a high suspicion and order imaging studies as needed, especially in the setting of trauma, or a recent procedure in the vicinity of the renal parenchyma.

Penile Agenesis Associated with Anorectal Malformation and Bilateral Renal Agenesis: A Case Report and a Review of the Literature.

ABSTRACT: Penile agenesis is complete absence of the penis in an otherwise normal phenotypic and genotypic male at birth that results from failure of development of the genital tubercle. It is an extremely rare anomaly that may be associated with anomalies in other organ systems, the extent and severity of which may affect the prognosis. The management is challenging and may have far reaching implications for the individual and family. While gender reassignment with bilateral orchidectomy and feminising genitoplasty has been carried out for most patients, significant psychosexual and social issues related to the male identity may occur due to foetal or postnatal sex steroid imprinting. We report a neonate with penile agenesis with bilateral renal agenesis and anorectal malformation.

Müllerian anomalies in girls with congenital solitary kidney.

BACKGROUND: The prevalence of Müllerian anomalies (MA) among patients with congenital solitary functioning kidney (SFK) is not well defined. A delay in diagnosis of obstructive MA can increase the risk of poor clinical outcomes. This study describes the prevalence of MA in patients with congenital SFK. METHODS: A retrospective review was performed of patients within the Nationwide Children's Hospital system with ICD9 or ICD10 diagnostic codes for congenital SFK defined as either unilateral renal agenesis (URA) or multicystic dysplastic kidney (MCDK) and confirmed by chart review. Patients with complex urogenital pathology were excluded. Renal anomaly, MA, reason for and type of pelvic evaluation, and age of diagnosis of anomalies were evaluated. RESULTS: Congenital SFK occurred in 431 girls due to URA (209) or MCDK (222). Pelvic evaluation, most commonly by ultrasound for evaluation of abdominal pain or dysmenorrhea, occurred in 115 patients leading to MA diagnosis in 60 instances. Among 221 patients ages 10 years and older, 104 underwent pelvic evaluation and 52 were diagnosed with an MA of which 20 were obstructive. Isolated uterine or combined uterine and vaginal anomalies were the most common MA. MA were five-fold more common in patients with URA compared to MCDK. In 75% of patients, the SFK was diagnosed prior to the MA. CONCLUSIONS: The prevalence of MA in patients with congenital SFK was 24% among those age 10 years or older, and 38% were obstructive. This justifies routine screening pelvic ultrasound in girls with congenital SFK to improve early diagnosis.

Utility of kidney ultrasonography during initial evaluation of pediatric nephrotic syndrome.

BACKGROUND: Current guidelines note a gap in high-quality evidence regarding utility of kidney ultrasonography (KUS) during initial evaluation of nephrotic syndrome (NS) due to presumed minimal change disease (pMCD). However, KUS is frequently obtained at our institution. This retrospective chart review assessed incidence and impact of abnormal sonographic findings in these patients. METHODS: Patients 1-18 years, newly diagnosed at our institution with NS from pMCD between 2011 and 2021, were identified. Hypertension, urinalysis, kidney function, and steroid responsiveness data were collected. Imaging findings were abstracted from radiology reports. Clinical impact of KUS was defined by actions taken in response to KUS. RESULTS: A total of 173 patients identified with new NS; 98 met inclusion criteria. Of these, 54% had KUS during the initial encounter. Demographic and laboratory data did not differ between those with and without KUS. KUS were abnormal in 70% of studies: increased kidney echogenicity (39.6%) and nephromegaly (35.8%) were the most common abnormal findings. Other findings included decreased corticomedullary differentiation, lobular kidney contour, solitary simple kidney cyst, and mild unilateral hydronephrosis. Steroid resistance was not associated with either nephromegaly or abnormal echogenicity. CONCLUSIONS: Our data showed no clinically relevant ultrasound findings causing deviations from the standard of care for pMCD. There was no association between KUS findings and steroid resistance. These data suggest there is little to no benefit from routine KUS imaging in patients with pMCD upon initial presentation. A higher resolution version of the Graphical abstract is available as Supplementary information.