Non-radiological assessment of kidney stones using the kidney injury test (KIT), a spot urine assay

2020 ◽  
Vol 125 (5) ◽  
pp. 732-738 ◽  
Author(s):  
Joshua Y.C. Yang ◽  
Reuben D. Sarwal ◽  
Karina Ky ◽  
Vivian Dong ◽  
Marshall Stoller ◽  
...  
2021 ◽  
pp. 101854
Author(s):  
Leslie Bernal Charondo ◽  
Fadl Hamouche ◽  
Reuben D. Sarwal ◽  
Minnie M. Sarwal ◽  
Thomas Chi ◽  
...  

Author(s):  
Elayne Cristina Morais Rateke ◽  
Camila Matiollo ◽  
Emerita Quintina de Andrade Moura ◽  
Michelle Andrigueti ◽  
Claudia Maccali ◽  
...  

2017 ◽  
Vol 44 (8) ◽  
pp. 1239-1248 ◽  
Author(s):  
Hermine I. Brunner ◽  
Michael R. Bennett ◽  
Gaurav Gulati ◽  
Khalid Abulaban ◽  
Marisa S. Klein-Gitelman ◽  
...  

Objective.To delineate urine biomarkers that forecast response to therapy of lupus nephritis (LN).Methods.Starting from the time of kidney biopsy, patients with childhood-onset systemic lupus erythematosus who were diagnosed with LN were studied serially. Levels of 15 biomarkers were measured in random spot urine samples, including adiponectin, α-1-acid glycoprotein (AGP), ceruloplasmin, hemopexin, hepcidin, kidney injury molecule 1, monocyte chemotactic protein-1, lipocalin-like prostaglandin D synthase (LPGDS), transforming growth factor-β (TGF-β), transferrin, and vitamin D binding protein (VDBP).Results.Among 87 patients (mean age 15.6 yrs) with LN, there were 37 treatment responders and 50 nonresponders based on the American College of Rheumatology criteria. At the time of kidney biopsy, levels of TGF-β (p < 0.0001) and ceruloplasmin (p = 0.006) were significantly lower among responders than nonresponders; less pronounced differences were present for AGP, hepcidin, LPGDS, transferrin, and VDBP (all p < 0.05). By Month 3, responders experienced marked decreases of adiponectin, AGP, transferrin, and VDBP (all p < 0.01) and mean levels of these biomarkers were all outstanding (area under the receiver-operating characteristic curve ≥ 0.9) for discriminating responders from nonresponders. Patient demographics and extrarenal disease did not influence differences in biomarker levels between response groups.Conclusion.Low urine levels of TGF-β and ceruloplasmin at baseline and marked reduction of AGP, LPGDS, transferrin, or VDBP and combinations of other select biomarkers by Month 3 are outstanding predictors for achieving remission of LN. If confirmed, these results can be used to help personalize LN therapy.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Simerjot K Jassal ◽  
Jaclyn Bergstrom ◽  
Joachim Ix ◽  
Dena Rifkin ◽  
Elizabeth Barrett-Connor

Albuminuria is an early, non-invasive marker of kidney injury, and an independent, potentially modifiable, risk factor for cardiovascular disease. Between 1992-96, 1764 community-dwelling men and women 31-98 (mean 71) years old were assessed for albuminuria using spot urine albumin/creatinine ratio (ACR). Median (interquartile range) ACR was 12 (7-20) mg/g. ACR was repeated in 1997-99 (n=926; ACR 12 [7-20]), 1999-2002 (n=977; ACR 16 [9-32]) and 2003-05 (n=755; ACR 11 [6-20]) (Figure). In analyses limited to 977 participants with ACR measured at 1992-96 and 1999-2002 visits, mean 6.6 (range 4.5-9.5) years later, median change in ACR was 4 (-1-17) mg/g; ACR doubled or greater in 36%, halved or less in 10%, and was unchanged in 54%. Table shows change in ACR by baseline characteristics. Using logistic regression, only sex was associated with doubling of ACR (vs. less than doubling); OR 1.42 (95% CI 1.08-1.87, p=0.01) for women; age, blood pressure, and diabetes were not; none of these were associated with halving of ACR. Further studies of predictors of albuminuria may inform future interventions to modify albuminuria and mitigate kidney and cardiovascular risk.


2019 ◽  
Vol 8 (4) ◽  
pp. 499 ◽  
Author(s):  
Drew Watson ◽  
Joshua Y. C. Yang ◽  
Reuben D. Sarwal ◽  
Tara K. Sigdel ◽  
Juliane M. Liberto ◽  
...  

The current standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early-stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information on early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB-approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early-stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cell-free DNA (cfDNA), methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (high versus low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6–99.3%) and 94.1% (95% CI: 82.3–100%). In addition, in patients with normal renal function (estimated glomerular filtration rate (eGFR) ≥ 90), the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be detected by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.


2021 ◽  
Vol 6 (1) ◽  
pp. 1-10
Author(s):  
Natale Gapare De Santo ◽  
Carmela Bisaccia ◽  
Luca Salvatore De Santo

A total of 11 non-gouty popes out of 264 (4.1%) died of kidney stones (very probably calcium stones) between the years 34-2005 AD. The prevalence of kidney stones was lower than expected on the basis of recent population-based data. The discrepancy might be due to the changing nutritional habits. Causes of death included acute kidney injury, chronic kidney disease, and stroke. The disease was highly recurrent in 9 of 11 (88.1%). Recurrences were observed 1 to 30 years after the first attack. Mean age at death was 63.1 years, much shorter than expected in popes. Clinically recurrent back-flank-groin pain emerged as a hallmark indicator of kidney stones in the narratives. It was sometimes associated with fever, hematuria, purulent urine and/or frequent urination and dysuria. Some popes were obese, sedentary, voracious and wine drinkers; others were lean, took long walks, ate frugal meals and practiced restraint when it came to drinking alcohol. They were cured with bed rest, diets, donkey milk, mineral waters, decongestant, purgatives, thermal baths, blood-letting, and surgery.


chronic kidney disease stages, Malnutrition, Nephrotic, Renal transplantation, acute kidney injury, Kidney stones


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mette Viberg Østergaard ◽  
Rune Ida ◽  
Annemarie Aarup Pedersen ◽  
Thomas Secher ◽  
Frederikke Emilie Sembach ◽  
...  

Abstract Background and Aims Diabetic nephropathy (DN) is a long-term complication that occurs in ∼40% of diabetes patients and is a leading cause of end-stage renal disease. Despite recent emergence of SGLT2 inhibitors and GLP-1 receptor agonists for nephroprotection in diabetes patients, drug discovery has been halted by the lack of reliable rodent models exhibiting features of human DN. In a newly established mouse model of progressive DN, we investigate the effects of hypertension on kidney injury. Method Female db/db mice were uninephrectomized (UNx) at 8 weeks of age and injected i.v. with a Renin adeno-associated virus (AAV) construct at different doses to induce hypertension, while a LacZAAV construct was used as negative control. db/+ mice served as healthy controls. Hypertension was measured by tail cuff and glomerular filtration rate (GFR) transcutaneous recoding of FITC-sinistrin after i.v. bolus injection at 22 weeks of age. Urine ACR measured in spot urine samples collected before termination 24 weeks of age. Terminal kidney samples were collected for 3D image analyses, histopathological evaluation, and next generation sequencing for gene expression analyses. Results GFR measurements indicated hyperfiltration in all AAV-injected UNx db/db mice compared to db/+ mice, while ReninAAV tended to dose-dependently decrease GFR compared to LacZAAV in UNx db/db mice. Urine ACR was worsened by ReninAAV-induced hypertension compared to LacZAAV controls. Automized AI-based glomerulosclerosis scoring showed ReninAAV dose-dependent increases in glomerulosclerosis compared to LacZAAV controls. 3D kidney imaging demonstrated increased glomerular volume in LacZAAV UNx db/db mice compared to db/+ mice with no further effect in ReninAAV groups. RNA sequencing revealed upregulated gene expression markers of fibrogenesis (incl. Col1a1, Col3, Col4, Fn1, Lamc2 and Vim) and tubular injury markers (Ngal and Kim-1), as well as downregulation of proximal tubular markers (Megalin and Aqp1) in ReninAAV UNx db/db mice compare to LacZAAV controls. Conclusion ReninAAV-induced hypertension in female UNx db/db mice accelerates kidney injury in uninephrectomized db/db mice and aggravates GFR, albuminuria and glomerulosclerosis in parallel with increased expression of genes associated with tubular injury renal fibrosis. Together, these data confirm that ReninAAV UNx db/db mice is a reliable model of DN with features of late stage human disease.


2019 ◽  
Vol 20 (18) ◽  
pp. 4463 ◽  
Author(s):  
Joshua Y. C. Yang ◽  
Reuben D. Sarwal ◽  
Fernando C. Fervenza ◽  
Minnie M. Sarwal ◽  
Richard A. Lafayette

Standard methods for detecting and monitoring of IgA nephropathy (IgAN) have conventionally required kidney biopsies or suffer from poor sensitivity and specificity. The Kidney Injury Test (KIT) Assay of urinary biomarkers has previously been shown to distinguish between various kidney pathologies, including chronic kidney disease, nephrolithiasis, and transplant rejection. This validation study uses the KIT Assay to investigate the clinical utility of the non-invasive detection of IgAN and predicting the progression of renal damage over time. The study design benefits from longitudinally collected urine samples from an investigator-initiated, multicenter, prospective study, evaluating the efficacy of corticosteroids versus Rituximab for preventing progressive IgAN. A total of 131 urine samples were processed for this study; 64 urine samples were collected from 34 IgAN patients, and urine samples from 64 demographically matched healthy controls were also collected; multiple urinary biomarkers consisting of cell-free DNA, methylated cell-free DNA, DMAIMO, MAMIMO, total protein, clusterin, creatinine, and CXCL10 were measured by the microwell-based KIT Assay. An IgA risk score (KIT-IgA) was significantly higher in IgAN patients as compared to healthy control (87.76 vs. 14.03, p < 0.0001) and performed better than proteinuria in discriminating between the two groups. The KIT Assay biomarkers, measured on a spot random urine sample at study entry could distinguish patients likely to have progressive renal dysfunction a year later. These data support the pursuit of larger prospective studies to evaluate the predictive performance of the KIT-IgA score in both screening for non-invasive diagnosis of IgAN, and for predicting risk of progressive renal disease from IgA and utilizing the KIT score for potentially evaluating the efficacy of IgAN-targeted therapies.


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