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Background: The human phospholipase B-II precursor (HPLBII-P) was originally purified from white blood cells but is also found in other cellular structures, such as kidney glomeruli and tubuli. The objective of this report was to investigate the relationship of HPLBII-P in urine to acute kidney injury in patients with COVID-19. Methods: Urine was collected at admission from 132 patients with COVID-19 admitted to the intensive care units (ICUs) because of respiratory failure. HPLBII-P was measured using a sensitive ELISA. For comparison, human neutrophil lipocalin (HNL) was measured in urine, using the ELISA configured with the monoclonal antibody 763/8F, as a sign of tubular affection in addition to routine biomarkers of kidney disease. Results: Overall, the concentrations of urinary HPLBII-P were almost 3-fold higher in patients with COVID-19 compared to healthy controls (p < 0.0001) and with significantly higher concentrations even in patients with COVID-19 without signs of acute kidney injury (AKI) (p < 0.001). HPLBII-P was further increased in patients with AKI (p < 0.02). HPLBII-P was significantly increased in patients with diabetes mellitus (p = 0.0008) and correlated to plasma glucose (r = 0.29, p = 0.001) and urine albumin concentrations (r = 0.55, p < 0.001). Conclusions: Urine concentrations of HPLBII-P are highly raised in the urine of patients with COVID-19 and relate to AKI and diabetes mellitus. HPLBII-P may reflect glomerular injury and/or increased glomerular cell activity in SARS-CoV-2 infections.

One of the supplements used in exercise programs are branched-chain amino acids (BCAAs), which are preferred because of their effect on the regeneration of muscle protein synthesis. However, due to their properties, BCAAs increase their amount in the blood in a short time. In this case the result may increase the workload of the kidneys. Based on the information, this study investigated the effects of resistance exercise and BCAA supplements on kidney tissue. Methods: A total of 24 Wistar Albino male rats were equally divided into 4 groups: Control, BCAA, Exercise and Exercise + BCAA. In the six-week study, resistance swimming exercise was applied to the exercise groups. BCAA supplementation was given to BCAA groups at 2.5 mg/kg doses before exercise. At the end of the study, histological, immunochemical and RT-PCR analyzes were performed. Results: As a result of the findings, it was found that the use of BCAA supplements together with exercise caused tubular necrosis (p=0.002). There was a significant increase in caspase 3 IHC staining findings in BCAA and Exercise + BCAA groups compared to the control group (p=0.011; p=0.02). In addition, KIM-1 expression levels were higher in the Exercise group than in all other groups (p=0.004; p = 0.003; p=0.008). Conclusion: As a result, BCAA consumption with resistance exercise caused damage to kidney tissue., Uno de los suplementos utilizados en los programas de ejercicio son los aminoácidos de cadena ramificada (BCAA), los cuales son preferidos por su efecto en la regeneración de la síntesis de proteínas musculares. Sin embargo, debido a sus propiedades, los BCAA aumentan su cantidad en la sangre en poco tiempo. En este caso, el resultado puede aumentar la carga de trabajo de los riñones. Con base en la información, este estudio investigó los efectos del ejercicio de resistencia y los suplementos de BCAA en el tejido renal. Métodos: Un total de 24 ratas macho Wistar Albino se dividieron por igual en 4 grupos: Control, BCAA, Ejercicio y Ejercicio + BCAA. En el estudio de seis semanas, se aplicó ejercicio de natación de resistencia a los grupos de ejercicio. La suplementación con BCAA se administró a grupos de BCAA en dosis de 2,5 mg/kg antes del ejercicio. Al final del estudio, se realizaron análisis histológicos, inmunoquímicos y RT-PCR. Resultados: Como resultado de los hallazgos se encontró que el uso de suplementos de BCAA junto con el ejercicio provocó necrosis tubular (p=0.002). Hubo un aumento significativo en los hallazgos de tinción IHC de caspasa 3 en los grupos BCAA y Ejercicio + BCAA en comparación con el grupo de control (p = 0,011; p = 0,02). Además, los niveles de expresión de KIM-1 fueron más altos en el grupo de ejercicio que en todos los demás grupos (p = 0,004; p = 0,003; p = 0,008). Conclusión: Como resultado, el consumo de BCAA con ejercicio de resistencia causó daño al tejido renal.

The objective of this prospective follow-up trial was to ascertain whether the urinary kidney injury molecule-1 (uKIM-1) associates with tumor tissue (tKIM-1) expression and with the pathological characteristics of clear renal cell carcinoma (cRCC) in radically nephrectomized (RN) and/or in partially nephrectomized (PN) patients with cRCC, pre- and postoperatively. This clinical study included 40 patients subjected to RN/PN (cRCC group) and 30 healthy volunteers (control group). Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit and normalized by urinary creatinine. Immunohistochemical staining (monoclonal anti-human anti-TIM-1/KIM-1/HAVCR antibody) was used for semiquantitative analysis of the tKIM-1 expression and expressed as a score (% KIM-1 positively stained tubules). Both markers were interpreted in terms of the tumor characteristics comprising tumor size, Fuhrman grade, pathological (pT) stage, tumor/nodes/metastasis (TNM) stage, lymphovascular invasion and type of surgery RN/PN. Preoperative uKIM-1 was significantly higher in the cRCC group compared to controls, such as uKIM-1 was statistically higher in RN than in PN patients. Postoperatively, uKIM-1 decreased to control values. Expression of tKIM-1 was documented in all nephrectomized patients. Significant associations were achieved between uKIM-1 and tKIM-1 and with considered tumor characteristics, especially with tumor size and grade. Based on the accomplished associations, we found uKIM-1 as a highly sensitive marker for cRCC diagnosis. The clinical trial registration number: 1110-2012.

Da se utvrdi razliku između gadolinijumskog i jodnog kontrasta u nastanku subkliničkog oštećenja bubrega iskazanog novim biomarkerima (NGAL i KIM). Da se ispita pojava eventualnog kliničkog oštećenja bubrega u populaciji dece sa normalnom bubrežnom funkcijom posle primene gadolinijumskog i jodnog kontrasta kao i mogućnost njenog što ranijeg otkrivanja upotrebom novih biomarkera, serumskog i urinarnog NGAL-a i urinarnog KIM-1. Da se evaluira eventualni uticaj intravenske hidracije pre i posle primene kontrasta na nastanak bubrežnog oštećenja kod dece sa normalnom bubrežnom funkcijom. Da se razmotri uticaj doze primenjenog kontrasta kao i istovremene primene antihipertenzivne terapije na nastanak bubrežnog oštećenja Metodologija: Naše prospektivno istraživanje je obavljeno kod 123 dece i adolescenata kod kojih su primenjene dve vrste kontrastnih snimanja u periodu od 1. januara 2013 godine do 31 decembra 2015 godine. Prva grupa (n=58) pacijenata sa acijanogenim urođenim srčanim manama je tokom angiografije primala nisko osmolarni, ne-jonski kontrast na bazi joda (iopromide, Ultravist® 370). Drugu grupu (n=65) su sačinjavali pacijenti sa suspektnim anomalijama urotrakta, bilo izvodnog sistema, bilo krvnih sudova bubrega kojima je rađena MR angiografija/urografija sa primenom gadolinijumskog kontrasta (gadopentetate dimeglumine, Magnevist®). Svakom pacijentu su uzimani uzorci urina pre snimanja (unutar 24h od snimanja, 0h), zatim posle 4, 24 i 48 sati od primenjenog kontrasta. Uzorci seruma su uzimani tri puta: pre snimanja, posle 24 i 48 sati od primenjene kontrastne procedure. Pored standardnih laboratorijskih parametara, u navedenim uzorcima su metodom ELISA određivani i serumski cistatin C, serumski i urinarni NGAL i urinarni KIM-1. Rezultati: Pacijenti koji su primili iopromide (n=58) su imali izraženiji pad eGFR posle 24 h (ΔGFR 10,77 (21,24) ml/min/1,73m2) u poređenju sa pacijentima koji su kao kontrasno sredstvo primili Gd-DTPA (n=65), (ΔGFR 5,93 (21,23) ml/min, To determine the difference between gadolinium and iodine contrast media in the development of subclinical kidney damage expressed with new biomarkers (NGAL and KIM). To investigate the possible occurrence of acute kidney injury in children with normal renal function after administration of iodinated and gadolinium based contrast and investigation the possibility of its early detection by using new biomarkers, such serum and urinary NGAL and urinary KIM-1. Also, to evaluate the possible effect of intravenous hydration before and after contrast on kidney function in children with normal renal function. And, to assess the impact of the dose of administered contrast media, as well as, evaluation of concomitant antihypertensive therapy on the possible renal impairment in children with normal kidney function. Material and Methods: We performed a prospective study of 123 children and adolescents undergoing contrast media exposure in a single center from January 1st, 2013 to December 31st, 2015. The first group (n=58) of patients with acyanotic congenital heart disease were undergoing angiography with low osmolar non-ionic, iodine based contrast administration (iopromide, Ultravist® 370). The second one (n=65) consisted of patients with suspected urinary tract anomalies who were undergoing MR angiography/urography with gadolinium based contrast administration (gadopentetate dimeglumine, Magnevist®). For each patient, four urine samples were obtained that corresponded to time 0 h (within 1-day pre contrast exposure), 4, 24 and 48 hours after procedure. The serum samples were obtained three times: within 1-day pre contrast exposure, 24 and 48 hours after procedure. In addition to standard laboratory parameters, serum cystatin C, serum and urinary NGAL and urinary KIM-1 were determined by ELISA. Results: Patients who have received iopromide (n = 58) had a more pronounced decrease eGFR after 24 h (ΔGFR 10.77 (21.24) ml / min / 1.73m2) as compared to patients who received a Gd

Diabetic nephropathy is a chronic complication of type 2 diabetes mellitus (DM). To prevent the onset or progression of nephropathy, a biomarker is needed that can detect kidney problems at an early stage. This study aims to determine differences in urine KIM-1 levels and correlation of levels of KIM-1 with albuminuria in patients with Non-Nephropathy DM, Insipien Nephropathy and Diabetic Nephropathy and the role of KIM-1 as an early biomarker of Diabetic Nephropathy. This research was conducted at Dr. Wahidin Sudirohusodo and his networking hospital. This study used a cross-sectional design with the number of type 2 DM patients as many as 78 people who met the inclusion criteria. The results showed that KIM-1 levels in patients with Non-Nephropathy DM (albuminuria [uALB] <20 mg/L), Ineffective Nephropathy (uALB 20-300 mg / L) and Diabetic Nephropathy (uALB> 300 mg/L) respectively is 0.862 ± 0.246 ng / mL, 2.409 ± 0.816 ng/mL and 3.503 ± 0.370 ng / mL. There were differences in mean KIM-1 levels between Non Nephropathy and Nephropathy Insipid (sig = 0.000 p <0.05), Non Nephropathy and Diabetic Nephropathy (sig = 0.000 p <0.05), Insipid Nephropathy and Diabetic Nephropathy (sig = 0.000 p <0.05) Correlation between KIM-1 level with albuminuria concentration in patients with Non Nephropathy DM (r = 0.948; sig <0.05), Nephropathy Insipien (r = 0.969; sig <0.05) and Diabetic Nephropathy (r = 0.911; sig <0.05). There are levels of KIM-1 that exceed the normal limit (> 0.837 ng / mL) in patients with non-nephropathy DM (normoalbuminuria) so that KIM-1 can be considered as an early biomarker of diabetic nephropathy., Nefropati Diabetik merupakan komplikasi kronis dari Diabetes Melitus (DM) tipe 2. Untuk mencegah timbulnya atau progresi nefropati maka dibutuhkan biomarker yang dapat mendeteksi adanya gangguan ginjal pada tahap dini. Penelitian ini bertujuan mengetahui perbedaan kadar KIM-1 urin dan korelasi kadar KIM-1 dengan albuminuria pada pasien DM Non Nefropati, Insipien Nefropati dan Nefropati Diabetik serta peran KIM-1 sebagai biomarker dini Nefropati Diabetik. Penelitian ini dilakukan di Rmah Sakit Umum Dr. Wahidin Sudirohusodo dan rumah sakit jejaringnya. Penelitian ini menggunakan desain cross sectional dengan jumlah pasien DM tipe 2 sebanyak 78 orang yang memenuhi kriteria inklusi. Hasil penelitian menunjukkan bahwa kadar KIM-1 pada pasien DM Non Nefropati (albuminuria [uALB] <20 mg/L), Insipien Nefropati (uALB 20-300 mg/L) dan Nefropati Diabetik (uALB >300 mg/L) berturut-turut adalah 0.862±0.246 ng/mL, 2.409±0.816 ng/mL dan 3.503±0.370 ng/mL. Terdapat perbedaan rerata kadar KIM-1 antara DM Non Nefropati dan Insipien Nefropati (sig=0.000 p<0.05), DM Non Nefropati dan Nefropati Diabetik (sig=0.000 p<0.05), Insipien Nefropati dan Nefropati Diabetik (sig=0.000 p<0.05). Korelasi antara kadar KIM-1 dengan konsentrasi albuminuria pada pasien DM Non Nefropati (r= 0.948; sig<0.05), Insipien Nefropati (r= 0.969; sig<0.05) dan Nefropati Diabetik (r= 0.911; sig<0.05). Terdapat kadar KIM-1 yang melewati batas normal (>0.837 ng/mL) pada pasien DM Non Nefropati (normoalbuminuria) sehingga KIM-1 dapat dipertimbangkan sebagai biomarker dini Nefropati Diabetik.

_Background:_ Acute kidney injury (AKI) is a frequently encountered complication of imported Plasmodium falciparum infection. Markers of structural kidney damage have been found to detect AKI earlier than serum creatinine-based prediction models but have not yet been evaluated in imported malaria. This pilot study aims to explore the predictive performance of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for AKI in travellers with imported P. falciparum infection. _Methods:_ Thirty-nine patients with imported falciparum malaria from the Rotterdam Malaria Cohort with available serum and urine samples at presentation were included. Ten of these patients met the criteria for severe malaria. The predictive performance of NGAL and KIM-1 as markers for AKI was compared with that of serum creatinine. _Results:_ Six of the 39 patients (15 %) developed AKI. Serum and urine NGAL and urine KIM-1 were all found to have large areas under the receiver operating characteristics curves (AUROC) for predicting AKI. Urine NGAL was found to have an excellent performance with positive predictive value (PPV) of 1.00 (95 % CI 0.54-1.00), a negative predictive value (NPV) of 1.00 (95 % CI 0.89-1.00) and an AUROC of 1.00 (95 % CI 1.00-1.00). _Conclusion:_ A good diagnostic performance of NGAL and KIM-1 for AKI was found. Particularly, urine NGAL was found to have an excellent predictive performance. Larger studies are needed to demonstrate whether these biomarkers are superior to serum creatinine as predictors for AKI in P. falciparum malaria.

Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails. Along the entire transplantation time course, there is a great demand for novel immune and nonimmune injury biomarkers. The use of these markers can be of great help in the monitoring of kidney injury in potential kidney donors, where acute kidney damage can be overlooked, in predicting acute transplant dysfunction during the early post-transplant periods, or in predicting chronic changes in long term followup. Numerous investigations have demonstrated that biomarkers that have the highest predictive value in acute kidney injury include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that the ideal biomarker to fulfill all the needs in renal transplant has not been identified yet. Although, in many animal models, new biomarkers are emerging for predicting acute and chronic allograft damage, in human allograft analysis they are still not routinely accepted and renal biopsy still remains the gold standard.

Karcinom bubrega (KB) čini približno 3,8% od ukupnog broja maligniteta kod odraslih, pokazujući konstantan porast poslednjih 30 godina. Najčešći i najagresivniji podtip KB je svetloćelijski karcinom bubrega (sKB), koji se često karakteriše odsustvom ranih simptoma i znakova bolesti, kao i laboratorijskih abnormalnosti. Pouzdan urinarni test za sKB mogao bi da ima značaj u preoperativnoj dijagnozi ovog tumora i kao dodatni marker za odgovor na terapiju i post-terapijsko praćenje. Sprovedena ispitivanja su ukazala na povećanu ekspresiju određenih proteina u tumorskom tkivu sKB. Na osnovu potencijala za urinarnu ekskreciju ovih ushodno regulisanih proteina, kao i senzitivnosti i specifičnosti za dijagnozu sKB, izdvojili su se protein 1 oštećenja bubrega (KIM-1) i akvaporin 1 (AQP-1). Cilj studije je bio da se ispita potencijal KIM-1 i AQP-1 za dijagnozu sKB, posebno tumorskih promena promera do 4 cm, kao i povezanost njihove koncentracije u urinu sa histološkim karakteristikama tumora. U studiju je bio uključen 41 pacijent (26 muškaraca, 15 žena), kod kojih je nakon parcijalne ili radikalne nefrektomije postavljena dijagnoza sKB. Kontrolnu grupu činilo je 40 zdravih ispitanika. Koncentracija oba biomarkera u urinu određena je primenom komercijalnog ELISA testa. Ekspresija KIM-1 u tumorskom tkivu određena je primenom TIM-1/KIM-1/HAVCR antitela. Rezultati ove studije su pokazali da određivanje koncentracije KIM-1 u urinu kod pacijenata sa sumnjom na postojanje sKB, predstavlja senzitivan i specifičan test za preoperativnu dijagnozu bolesti i da značajno korelira sa stadijumom i gradusom tumora. Određivanje koncentracije KIM-1 u urinu predstalja dodatni dijagnostički test za utvrđivanje prirode malih tumorskih promena promera do 4 cm. Poređenjem koncentracija KIM-1 u urinu izraženim u apsolutnim i korigovanim vrednostima, nije pokazana statistički značajna razlika u dijagnostičkom potencijalu. Tkivna ekspresija KIM-1 statistički značajno korelira sa stadijumom tumora i vi, Renal cell carcinoma (RCC) represents approximately 3.8% of all malignancies in adults, increasing permanently over the past 30 years. The most common and also the most aggressive subtype of RCC is clear renal cell carcinoma (cRCC), often characterized by lack of early symptoms, signs and laboratory abnormalities. A reliable urine test for cRCC could have importance in the preoperative diagnosis of this tumor as an additional marker for the monitoring of response to therapy and for the post-treatment surveillance, as well. Recent studies have shown the increased expression of certain proteins in tumor tissue of cRCC. Based on the potential for urinary excretion of these up-regulated proteins, as well as the sensitivity and specificity for the diagnosis of cRCC, the kidney injury molecul 1 (KIM-1) and aquaporin 1 (AQP-1) have a special significance. The aim of this study was to investigate the potential of KIM-1 and AQP-1 for the diagnosis of cRCC, especially lesion diameter up to 4 cm, and the linkage of their concentration in urine and histological characteristics of the tumor. The study involved 41 patients (26 men, 15 women), who underwent the partial or radical nephrectomy and diagnosed cRCC. The control group consisted of 40 healthy subjects. The concentration of both biomarkers in the urine was determined by commercially available ELISA kits. Expression of KIM-1 in the tumor tissue is determined by applying the TIM-1/KIM-1/HAVCR antibody. Results of this study showed that the determination of the concentration of KIM-1 in the urine of patients with suspected cRCC is sensitive and specific test for the preoperative diagnosis of the disease and significantly correlated with tumor stage and grade. Determination of KIM-1 in urine represented a further diagnostic test to determine the nature of small lesion sizes up to 4 cm. By comparing the concentration of KIM-1 in urine expressed in absolute and corrected values, we did not show statistically significant differe

Tato bakalářská práce se zabývá diagnostikou akutního poškození ledvin. V úvodu této práce je stručně popsána charakteristika, klasifikace a hlavní příčiny akutního poškození ledvin. Zbytek práce se věnuje diagnostice hlavních biomarkerů akutního poškození ledvin, zaměřené na popis funkce a stanovení kreatininu, urey a glomerulární filtrace, a především na popis struktury, funkce a diagnostiky nových biomarkerů, kterými jsou například NGAL (Neutrophil Gelatinase-Associated Lipocalin), KIM-1 (Kidney Injury Molecule-1), interleukin-18 či cystatin C., This bachelor thesis is focused on the diagnosis of the acute kidney injury. At the beginning the description, classification and major causes of acute kidney injury have been described briefly. The next part of the bachelor thesis has been aimed at diagnosis of main biomarkers of acute kidney injury, especially at the description of function and determination of creatinine, urea and glomerular filtration. In addition, the structure, function and determination of new biomarkers has been described e.g. NGAL (Neutrophil Gelatinase-Associated Lipocalin), KIM-1 (Kidney Injury Molecule-1), interleukin-18 and cystatin C., Katedra biologických a biochemických věd, 1. Prezentace výsledků bakalářské práce. 2. Diskuze k posudku vedoucího bakalářské práce. 3. Studentka zodpověděla vaechny dotazy a připomínky k BP.

Because of the difficulty in detecting segment-specific response in the kidney, we investigated the molecular events underlying acute kidney injury in the proximal tubules of rats with cisplatin (cis-diamminedichloroplatinum II)-induced nephrotoxicity. Microarray analysis revealed that mRNA levels of several cytokines and chemokines, such as interleukin-1beta, chemokine (C-C motif) ligand (CCL) 2, CCL20, chemokine (C-X-C motif) ligand (CXCL) 1, and CXCL10 were significantly increased after cisplatin treatment in both isolated proximal tubules and whole kidney. Interestingly, tubular CCL2 mRNA levels increased soon after cisplatin administration, whereas CCL2 mRNA levels in whole kidney first decreased and then increased. Levels of both CCL2 and kidney injury molecule-1 (KIM-1) in the whole kidney increased after cisplatin administration. Immunofluorescence analysis revealed CCL2 changes in the proximal tubular cells initially and then in the medullary interstitium. Urinary CCL2 excretion significantly increased approximately 3-fold compared with controls the day after cisplatin administration (5mg/kg), when no changes were observed plasma creatinine and blood urea nitrogen levels. Urinary levels of KIM-1 also increased 3-fold after cisplatin administration. In addition, urinary CCL2 rather than KIM-1 increased in chronic renal failure rats after administration of low-dose cisplatin (2mg/kg), suggesting that urinary CCL2 was selective for cisplatin-induced nephrotoxicity in renal impairment. These results indicated that the increase in cytokine and chemokine expression in renal epithelial cells might be responsible for kidney deterioration in cisplatin-induced nephrotoxicity, and that urinary CCL2 is associated with tubular injury and serves as a sensitive and noninvasive marker for the early detection of cisplatin-induced tubular injury.

Background: The predictive value of acute kidney injury (AKI) urinary biomarkers may depend on the time interval following tubular injury, thereby explaining in part the heterogeneous performance of these markers that has been reported in the literature. We studied the infl

BackgroundSeveral biomarkers are becoming available for the early detection of acute kidney injury (AKI), but few have been directly compared.ObjectiveTo compare urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl glucosaminidase (NAG) against serum creatinine and renal histological score in the initiation, maintenance, and recovery phases of cisplatin (CP)-induced AKI.MethodsSprague-Dawley rats (300-350 g) were injected once through their tail veins with CP (CP group) at 5.5 mg/kg or with same volume of normal saline vehicle (Control group). Rats were euthanized at 2, 4, 6, 12, and 24 hours, and on days 2, 3, 6, and 10 (n = 12 in the CP group and n = 6 in the Control group at each time point), and urine, blood, and kidney samples were analyzed.ResultsA significant increase in serum creatinine was noted by day 3 in the CP group versus Control group [1.46 (0.12) vs 0.28 (0.03) mg/dL; mean (SE); P < 0.05]. The renal histology scores for brush border loss and tubular necrosis were significantly higher at 12 and 24 hours, respectively, in the CP group. Urinary kidney injury molecule-1 levels were significantly higher at 24 hours in the CP group than in the Control group [48.26 (13.13) vs 8.21 (3.31) pg/mg creatinine; P < 0.05] and remained elevated through day 10. Both urine NAG and NGAL levels were significantly higher by day 2 in the CP than in the Control group [NAG, 8.19 (0.82) vs 3.48 (0.40) pg/mg creatinine, P G 0.05; NGAL, 2911.80 (368.10) vs 1412.60 (250.20) pg/mg creatinine, P < 0.05]. Urinary NAG remained elevated for 6 days and NGAL for 3 days.ConclusionsOur study suggests a temporal hierarchy in the ability of certain urinary protein-based biomarkers to detect AKI after a well-defined tubular injury. Comparative analyses of urinary biomarkers are warranted in clinical settings such as patients receiving CP to discern the time course and pattern of expression.

ObjectiveHIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women.MethodsIn the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes.ResultsCompared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (-0.15 mL/min per 1.73 m, P < 0.0001), IL-18 (-0.09 mL/min per 1.73 m, P < 0.0001) and KIM-1 (-0.06 mL/min per 1.73 m, P < 0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); ≥5% (1.88; 1.30 to 2.71); and ≥10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87).ConclusionsAmong HIV-infected women in the Women's Interagency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.

Introduction: Although serum creatinine is the standard metric tool for the detection of renal injury, its lack of sensitivity has made the early diagnosis of acute kidney injury (AKI) very difficult. In fact, the absence of sensitive AKI biomarkers has impaired progress in the nephrology field and had a detrimental effect on the design and outcome of AKI clinical trials. Recently, several proteins have shown potential in the early detection of acute and chronic kidney injuries. Areas covered: This review discusses the current status of kidney injury molecule-1 (KIM-1) as a potential diagnostic tool in patients with various acute and chronic kidney diseases. The focus is limited to human studies from January 2002 to July 2010. The review clarifies the clinical conditions for which KIM-1 has the greatest potential utility for early detection of kidney injury. It also demonstrates to the reader the barriers to the successful use of KIM-1 and other biomarkers in clinical practice, and the future trials that will be needed to validate their use. Expert opinion: Despite the early promise of biomarkers such as KIM-1 for the early detection and prognosis of kidney disease, more studies are required to establish their utility in clinical practice. Indeed, the published clinical studies of urine KIM-1 so far are small and insufficient to support clinical studies of urine KIM-1 as an effective AKI diagnostic test in humans. It is suggested, through the heterogeneity of AKI and existing published data, that more than one biomarker may be necessary to obtain sufficient sensitivity and specificity for AKI screening.

Cadmium ( Cd) exposure results in injury to the proximal tubule characterized by polyuria and proteinuria. Kidney injury molecule-1 ( Kim-1) is a transmembrane glycoprotein not normally detected in the mature kidney, but is upregulated and shed into the urine following nephrotoxic injury. In this study, we determine if Kim-1 might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. Weekly urine samples were analyzed for Kim-1, protein, creatinine, metallothionein, and Clara cell protein CC-16. Significant levels of Kim-1 were detected in the urine by 6 weeks and continued to increase throughout the treatment period. This appearance of Kim-1 occurred 4-5 weeks before the onset of proteinuria, and 1-3 weeks before the appearance of metallothionein and CC-16. Higher doses of Cd gave rise to higher Kim-1 excretion. Reverse transcriptase-polymerase chain reaction ( RT-PCR) expression analysis showed that Kim-1 transcript levels were increased after 6 weeks at the low dose of Cd. Immunohistochemical analysis showed that Kim-1 was present in proximal tubule cells of the Cd-treated rats. Our results suggest that Kim-1 may be a useful biomarker of early stages of Cd-induced proximal tubule injury.

Callan, A.C., Devine, A., Qi, L., Ng, J.C., Hinwood, A.L. (2015). Investigation of the relationship between low environmental exposure to metals and bone mineral density, bone resorption and renal function in International Journal of Hygiene and Environmental Health, 218(5), 444-451. Available here.