Urinary Excretion of Kidney Injury Molecule -1 in Renal Transplant Recipients

N1-methylnicotinamide (N1-MN) and N1-methyl-2-pyridone-5-carboxamide (2Py) are successive end products of NAD+ catabolism. N1-MN excretion in 24-h urine is the established biomarker of niacin nutritional status, and recently shown to be reduced in renal transplant recipients (RTR). However, it is unclear whether 2Py excretion is increased in this population, and, if so, whether a shift in excretion of N1-MN to 2Py can be attributed to kidney function. Hence, we assessed the 24-h urinary excretion of 2Py and N1-MN in RTR and kidney donors before and after kidney donation, and investigated associations of the urinary ratio of 2Py to N1-MN (2Py/N1-MN) with kidney function, and independent determinants of urinary 2Py/N1-MN in RTR. The urinary excretion of 2Py and N1-MN was measured in a cross-sectional cohort of 660 RTR and 275 healthy kidney donors with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Linear regression analyses were used to investigate associations and determinants of urinary 2Py/N1-MN. Median 2Py excretion was 178.1 (130.3–242.8) μmol/day in RTR, compared to 155.6 (119.6–217.6) μmol/day in kidney donors (p < 0.001). In kidney donors, urinary 2Py/N1-MN increased significantly after kidney donation (4.0 ± 1.4 to 5.2 ± 1.5, respectively; p < 0.001). Smoking, alcohol consumption, diabetes, high-density lipoprotein (HDL), high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) were identified as independent determinants of urinary 2Py/N1-MN in RTR. In conclusion, the 24-h urinary excretion of 2Py is higher in RTR than in kidney donors, and urinary 2Py/N1-MN increases after kidney donation. As our data furthermore reveal strong associations of urinary 2Py/N1-MN with kidney function, interpretation of both N1-MN and 2Py excretion may be recommended for assessment of niacin nutritional status in conditions of impaired kidney function.

Download Full-text

Acute kidney injury in renal transplant recipients undergoing cardiac surgery

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa063 ◽

2020 ◽

Vol 36 (1) ◽

pp. 185-196

Author(s):

Gregory L Hundemer ◽

Anand Srivastava ◽

Kirolos A Jacob ◽

Neeraja Krishnasamudram ◽

Salman Ahmed ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Cardiac Surgery ◽

Risk Factor ◽

Renal Transplant ◽

Kidney Disease ◽

Kidney Injury ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Trough Levels

Abstract Background Acute kidney injury (AKI) is a key risk factor for chronic kidney disease in the general population, but has not been investigated in detail among renal transplant recipients (RTRs). We investigated the incidence, severity and risk factors for AKI following cardiac surgery among RTRs compared with non-RTRs with otherwise similar clinical characteristics. Methods We conducted a retrospective cohort study of RTRs (n = 83) and non-RTRs (n = 83) who underwent cardiac surgery at two major academic medical centers. Non-RTRs were matched 1:1 to RTRs by age, preoperative (preop) estimated glomerular filtration rate and type of cardiac surgery. We defined AKI according to Kidney Disease: Improving Global Outcomes criteria. Results RTRs had a higher rate of AKI following cardiac surgery compared with non-RTRs [46% versus 28%; adjusted odds ratio 2.77 (95% confidence interval 1.36–5.64)]. Among RTRs, deceased donor (DD) versus living donor (LD) status, as well as higher versus lower preop calcineurin inhibitor (CNI) trough levels, were associated with higher rates of AKI (57% versus 33% among DD-RTRs versus LD-RTRs; P = 0.047; 73% versus 36% among RTRs with higher versus lower CNI trough levels, P = 0.02). The combination of both risk factors (DD status and higher CNI trough level) had an additive effect (88% AKI incidence among patients with both risk factors versus 25% incidence among RTRs with neither risk factor, P = 0.004). Conclusions RTRs have a higher risk of AKI following cardiac surgery compared with non-RTRs with otherwise similar characteristics. Among RTRs, DD-RTRs and those with higher preop CNI trough levels are at the highest risk.

Download Full-text