Standardized urine biomarkers in assessing neonatal kidney function: are we there yet?

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV–) men. Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV– men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR. Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV– men. Among HIV+ men, the highest vs. lowest tertiles of albumin (–1.78 mL/min/1.73 m2/year, 95% CI –3.47 to –0.09) and α1m (–2.43 mL/min/1.73 m2/year, 95% CI –4.14 to –0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV– men, the highest vs. lowest tertile of α1m (–2.49 mL/min/1.73 m2/year, 95% CI –4.48 to –0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus. Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.

Download Full-text

Nephrotoxic Metal Mixtures and Preadolescent Kidney Function

Children ◽

10.3390/children8080673 ◽

2021 ◽

Vol 8 (8) ◽

pp. 673

Author(s):

Yuri Levin-Schwartz ◽

Maria D. Politis ◽

Chris Gennings ◽

Marcela Tamayo-Ortiz ◽

Daniel Flores ◽

...

Keyword(s):

Kidney Function ◽

Cystatin C ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Metal Mixtures ◽

Media Type ◽

Mixture Effects ◽

Mexican Children ◽

Urine Biomarkers ◽

Combining Information

Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4–6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8–10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and −2.6% (95% CI: −5.1%, −0.1%) and −3.3% (95% CI: −6.5%, −0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses.

Download Full-text

The effect of antenatal indomethacin on extremely preterm neonatal kidney function

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.1080/14767058.2020.1869933 ◽

2021 ◽

pp. 1-8

Author(s):

Christine Brichta ◽

Kara K. Hoppe ◽

Michael R. Lasarev ◽

Matthew W. Harer

Keyword(s):

Kidney Function ◽

Extremely Preterm ◽

Neonatal Kidney

Download Full-text

Effect of Successive Gentamicin and Amikacin Therapies on Renal Function of Neonates

10.21203/rs.3.rs-434051/v1 ◽

2021 ◽

Author(s):

Bonifasius Siyuka Singu ◽

Milka Ndapandula Ndeunyema ◽

Ene Ikpong Ette ◽

Clarissa Hildegard Pieper ◽

Roger Karel Verbeeck

Keyword(s):

Kidney Function ◽

Pharmacokinetic Analysis ◽

Intravenous Bolus ◽

First Line ◽

Second Line Therapy ◽

Blood Samples ◽

Line Therapy ◽

Other Information ◽

Nephrotoxic Drugs ◽

Neonatal Kidney

Abstract Gentamicin and amikacin are aminoglycoside antibiotics which are renally excreted and known to cause nephrotoxicity. Neonatal eGFR per body surface area is lower than in adults and exposure to nephrotoxic drugs could lead to more suppression in kidney function. The aim of this study was to investigate the effect of administering successive courses of gentamicin (first-line) and amikacin (second-line) therapy on neonatal kidney function. Data were collected from patient records of neonates receiving gentamicin (July-December 2019) and amikacin (July-December 2020) at the Neonatal Unit of Windhoek Central Hospital (Namibia). 44 neonates on gentamicin and 35 on amikacin were included in this study. Aminoglycoside dose was administered as a slow intravenous bolus and two blood samples taken for pharmacokinetic analysis. Other information collected: gestational age, postnatal age (PNA), weight, height, serum creatinine, and dosage regimen. Primary outcomes were correlation of eGFR with PNA, and the time it took to clear the drug to < 1 µg/mL; eGFR was calculated using the Schwartz method. The negative correlation between eGFR and PNA was significant (r = -0.370, p = 0.034). Therapeutic range Cmax were achieved in 27.3% gentamicin neonates (15–25 µg/mL), and 17.1% in amikacin (55–65 µg/mL). Proportion of neonates with a Cmin <1 µg/mL within the 24-hour dosage interval were 72.7% and 82.9% for gentamicin and amikacin, respectively. Conclusion: The decline in kidney function for neonates while on amikacin was significant. However, a considerably high proportion of amikacin neonates (82.9%) were able to clear the drug to < 1 µg/mL within 24 hours.

Download Full-text

Longitudinal urinary biomarkers of immunological activation in covid-19 patients without clinically apparent kidney disease versus acute and chronic failure

Scientific Reports ◽

10.1038/s41598-021-99102-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Krzysztof Laudanski ◽

Tony Okeke ◽

Hajj Jihane ◽

Kumal Siddiq ◽

Daniel J. Rader ◽

...

Keyword(s):

Immune Response ◽

Kidney Disease ◽

Serum Level ◽

Kidney Function ◽

Immune Activation ◽

Critical Role ◽

Urinary Biomarkers ◽

Activation Markers ◽

Urine Biomarkers ◽

Immune System Activation

AbstractKidney function is affected in COVID-19, while kidney itself modulates the immune response. Here, hypothesize if COVID-19 urine biomarkers level can assess immune activation vs. clinical trajectory. Considering the kidney’s critical role in modulating the immune response, we sought to analyze activation markers in patients with pre-existing dysfunction. This was a cross-sectional study of 68 patients. Blood and urine were collected within 48 h of hospital admission (H1), followed by 96 h (H2), seven days (H3), and up to 25 days (H4) from admission. Serum level ferritin, procalcitonin, IL-6 assessed immune activation overall, while the response to viral burden was gauged with serum level of spike protein and αspike IgM and IgG. 39 markers correlated highly between urine and blood. Age and race, and to a lesser extend gender, differentiated several urine markers. The burden of pre-existing conditions correlated with urine DCN, CAIX and PTN, but inversely with IL-5 or MCP-4. Higher urinary IL-12 and lower CAIX, CCL23, IL-15, IL-18, MCP-1, MCP-3, MUC-16, PD-L1, TNFRS12A, and TNFRS21 signified non-survivors. APACHE correlated with urine TNFRS12, PGF, CAIX, DCN, CXCL6, and EGF. Admission urine LAG-3 and IL-2 predicted death. Pre-existing kidney disease had a unique pattern of urinary inflammatory markers. Acute kidney injury was associated, and to a certain degree, predicted by IFNg, TWEAK, MMP7, and MUC-16. Remdesavir had a more profound effect on the urine biomarkers than steroids. Urinary biomarkers correlated with clinical status, kidney function, markers of the immune system activation, and probability of demise in COVID-19.

Download Full-text