• Abstract

    Renal failure occurs when one or both kidneys are unable to function properly. It can be classified into two types: acute and chronic. Acute renal failure is a sudden and temporary condition, while chronic renal failure develops gradually and can lead to permanent kidney damage. Acute kidney injury arises when the kidneys lose their ability to filter waste from the bloodstream effectively. This can result in the accumulation of harmful waste products and an imbalance in the blood's chemical composition. Previously, acute renal failure was referred to as acute kidney injury. Hospitalized patients, particularly those requiring critical care, are at a higher risk of developing acute kidney injury. Chronic kidney disease (CKD), also referred to as chronic kidney failure, is characterized by a persistent decline in renal function. The kidneys play a vital role in filtering waste products and excess fluid from the blood to produce urine. In severe cases of chronic kidney disease, the body accumulates harmful levels of fluids, electrolytes, and waste products. While creatinine, urea, uric acid, and electrolytes are commonly analyzed as markers of kidney function, numerous studies have highlighted and validated the importance of alternative markers such as cystatin C and β-Trace Protein. Isocyanic acid reacts with the amino groups in haemoglobin to form Carbamylated Haemoglobin (CarHb). In the body, isocyanic acid is produced as a byproduct of urea dissociation. Patients with renal failure exhibit higher levels of Carbamylated Haemoglobin compared to healthy individuals. Furthermore, CarHb levels are lower in patients with acute kidney injury (AKI) than in those with chronic kidney disease (CKD). This indicates that as kidney disease progresses from an acute to a chronic stage, Carbamylated Haemoglobin levels increase. Therefore, Carbamylated Haemoglobin can serve as a potential marker for predicting the progression of renal failure

  • References

    1. Star R. A. (1998). Treatment of acute renal failure. Kidney international, 54(6), 1817–1831. https://doi.org/10.1046/j.1523-1755.1998.00210.x
    2. Van Biesen, W., Vanholder, R., & Lameire, N. (2006). Defining acute renal failure: RIFLE and beyond. Clinical journal of the American Society of Nephrology : CJASN, 1(6), 1314–1319. https://doi.org/10.2215/CJN.02070606
    3. Webster, A. C., Nagler, E. V., Morton, R. L., & Masson, P. (2017). Chronic Kidney Disease. Lancet (London, England), 389(10075), 1238–1252. https://doi.org/10.1016/S0140-6736(16)32064-5
    4. Abdel-Kader K. (2022). Symptoms with or because of Kidney Failure?. Clinical journal of the American Society of Nephrology : CJASN, 17(4), 475–477. https://doi.org/10.2215/CJN.02050222
    5. Lameire N. (2005). The pathophysiology of acute renal failure. Critical care clinics, 21(2), 197–210. https://doi.org/10.1016/j.ccc.2005.01.001
    6. Mehta, R. L., & Chertow, G. M. (2003). Acute renal failure definitions and classification: time for change?. Journal of the American Society of Nephrology : JASN, 14(8), 2178–2187. https://doi.org/10.1097/01.asn.0000079042.13465.1a
    7. Wynckel, A., Randoux, C., Millart, H., Desroches, C., Gillery, P., Canivet, E., & Chanard, J. (2000). Kinetics of carbamylated haemoglobin in acute renal failure. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 15(8), 1183–1188. https://doi.org/10.1093/ndt/15.8.1183
    8. Stark GR, Stein WH, Moore S. Reactions of the cyanate present in aqueous urea with amino acids and proteins. J Biol Chem. 1960;235:3177–81. https://doi.org/10.1016/S0021-9258(20)81332-5.
    9. DIRNHUBER, P., & SCHUTZ, F. (1948). The isomeric transformation of urea into ammonium cyanate in aqueous solutions. The Biochemical journal, 42(4), 628–632.
    10. Lee, C. K., & Manning, J. M. (1973). Kinetics of the carbamylation of the amino groups of sickle cell hemoglobin by cyanate. The Journal of biological chemistry, 248(16), 5861–5865.
    11. Flückiger, R., Harmon, W., Meier, W., Loo, S., & Gabbay, K. H. (1981). Hemoglobin carbamylation in uremia. The New England journal of medicine, 304(14), 823–827. https://doi.org/10.1056/NEJM198104023041406
    12. Jensen, M., Nathan, D. G., & Bunn, H. F. (1973). The reaction of cyanate with the alpha and beta subunits in hemoglobin. Effects of oxygenation, phosphates, and carbon dioxide. The Journal of biological chemistry, 248(23), 8057–8063.
    13. Nigen, A. M., Bass, B. D., & Manning, J. M. (1976). Reactivity of cyanate with valine-1 (alpha) of hemoglobin. A probe of conformational change and anion binding. The Journal of biological chemistry, 251(23), 7638–7643.
    14. Cerami, A., & Manning, J. M. (1971). Potassium cyanate as an inhibitor of the sickling of erythrocytes in vitro. Proceedings of the National Academy of Sciences of the United States of America, 68(6), 1180–1183. https://doi.org/10.1073/pnas.68.6.1180
    15. Kwan, J. T., Carr, E. C., Neal, A. D., Burdon, J., Raftery, M. J., Marsh, F. P., Barron, J. L., & Bending, M. R. (1991). Carbamylated haemoglobin, urea kinetic modelling and adequacy of dialysis in haemodialysis patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 6(1), 38–43. https://doi.org/10.1093/ndt/6.1.38
    16. Manning, J. M., Lee, C. K., Cerami, A., & Gillette, P. N. (1973). Gas chromatographic determination of the carbamylation of hemoglobin S by cyanate. The Journal of laboratory and clinical medicine, 81(6), 941–945.
    17. Kraus, A. P., Stephens, M. S., & Kraus, L. M. (1985, January). Carbamoylation of plasma-proteins in CAPD and HD. IN KIDNEY INTERNATIONAL (VOL. 27, NO. 1, PP. 181-181). 350 MAIN ST, MALDEN, MA 02148: BLACKWELL SCIENCE INC.
    18. Smith, W. G., Holden, M., Benton, M., & Brown, C. B. (1988). Carbamylated haemoglobin in chronic renal failure. Clinica chimica acta; international journal of clinical chemistry, 178(3), 297–303. https://doi.org/10.1016/0009-8981(88)90238-0
    19. Davenport, A., Jones, S., Goel, S., Astley, J. P., & Feest, T. G. (1996). Carbamylated hemoglobin: a potential marker for the adequacy of hemodialysis therapy in end-stage renal failure. Kidney international, 50(4), 1344–1351. https://doi.org/10.1038/ki.1996.447
    20. Stim, J., Shaykh, M., Anwar, F., Ansari, A., Arruda, J. A., & Dunea, G. (1995). Factors determining hemoglobin carbamylation in renal failure. Kidney international, 48(5), 1605–1610. https://doi.org/10.1038/ki.1995.454
    21. Oimomi, M., Nishimoto, S., Matsumoto, S., Hatanaka, H., Ishikawa, K., Kawasaki, T., Yoshimura, Y., & Baba, S. (1986). Carbamylated plasma protein in renal failure. Nihon Jinzo Gakkai shi, 28(3), 269–271.
    22. Smith, W. G., Holden, M., Benton, M., & Brown, C. B. (1988). Carbamylated haemoglobin in chronic renal failure. Clinica chimica acta; international journal of clinical chemistry, 178(3), 297–303. https://doi.org/10.1016/0009-8981(88)90238-0
    23. Balion, C. M., Draisey, T. F., & Thibert, R. J. (1998). Carbamylated hemoglobin and carbamylated plasma protein in hemodialyzed patients. Kidney international, 53(2), 488–495. https://doi.org/10.1046/j.1523-1755.1998.00777.x
    24. Han, J. S., Kim, Y. S., Chin, H. J., Jeon, U. S., Ahn, C., Kim, S., Lee, J. S., Jang, I. J., & Shin, S. G. (1997). Temporal changes and reversibility of carbamylated hemoglobin in renal failure. American journal of kidney diseases : the official journal of the National Kidney Foundation, 30(1), 36–40. https://doi.org/10.1016/s0272-6386(97)90562-x
    25. Wynckel, A., Randoux, C., Millart, H., Desroches, C., Gillery, P., Canivet, E., & Chanard, J. (2000). Kinetics of carbamylated haemoglobin in acute renal failure. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 15(8), 1183–1188. https://doi.org/10.1093/ndt/15.8.1183
    26. Tarif, N., Shaykh, M., Stim, J., Arruda, J. A., & Dunea, G. (1997). Carbamylated hemoglobin in hemodialysis patients. American journal of kidney diseases : the official journal of the National Kidney Foundation, 30(3), 361–365. https://doi.org/10.1016/s0272-6386(97)90280-8
    27. Hasuike, Y., Nakanishi, T., Maeda, K., Tanaka, T., Inoue, T., & Takamitsu, Y. (2002). Carbamylated hemoglobin as a therapeutic marker in hemodialysis. Nephron, 91(2), 228–234. https://doi.org/10.1159/000058397
    28. Tasanarong, A., Seublinvong, T., & Eiam-Ong, S. (2002). The role of carbamylated hemoglobin in identifying acute and chronic renal failure. Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 85(4), 462–469.
    29. Kalim, S., Tamez, H., Wenger, J., Ankers, E., Trottier, C. A., Deferio, J. J., Berg, A. H., Karumanchi, S. A., & Thadhani, R. I. (2013). Carbamylation of serum albumin and erythropoietin resistance in end stage kidney disease. Clinical journal of the American Society of Nephrology : CJASN, 8(11), 1927–1934. https://doi.org/10.2215/CJN.04310413
    30. Tang, M., Berg, A., Rhee, E. P., Allegretti, A. S., Nigwekar, S., Karumanchi, S. A., Lash, J. P., & Kalim, S. (2023). The Impact of Carbamylation and Anemia on HbA1c's Association With Renal Outcomes in Patients With Diabetes and Chronic Kidney Disease. Diabetes care, 46(1), 130–137. https://doi.org/10.2337/dc22-1399
    31. Drechsler, C., Kalim, S., Wenger, J. B., Suntharalingam, P., Hod, T., Thadhani, R. I., Karumanchi, S. A., Wanner, C., & Berg, A. H. (2015). Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease. Kidney international, 87(6), 1201–1208. https://doi.org/10.1038/ki.2014.429
    32. Koeth, R. A., Kalantar-Zadeh, K., Wang, Z., Fu, X., Tang, W. H., & Hazen, S. L. (2013). Protein carbamylation predicts mortality in ESRD. Journal of the American Society of Nephrology : JASN, 24(5), 853–861. https://doi.org/10.1681/ASN.2012030254
    33. Sabater, J., Quereda, C., Herrera, I., Pascual, J., Villafruela, J. J., & Ortuño, J. (1991). Nonenzymatic glycosylation of hemoglobin and total plasmatic proteins in end-stage renal disease. American journal of nephrology, 11(1), 37–43. https://doi.org/10.1159/000168270
    34. Berg, A. H., Drechsler, C., Wenger, J., Buccafusca, R., Hod, T., Kalim, S., Ramma, W., Parikh, S. M., Steen, H., Friedman, D. J., Danziger, J., Wanner, C., Thadhani, R., & Karumanchi, S. A. (2013). Carbamylation of serum albumin as a risk factor for mortality in patients with kidney failure. Science translational medicine, 5(175), 175ra29. https://doi.org/10.1126/scitranslmed.3005218
    35. Gorisse, L., Jaisson, S., Piétrement, C., & Gillery, P. (2022). Carbamylated Proteins in Renal Disease: Aggravating Factors or Just Biomarkers?. International journal of molecular sciences, 23(1), 574. https://doi.org/10.3390/ijms23010574
    36. Imamura, R., Okumi, M., Isaka, Y., Ichimaru, N., Moriyama, T., Imai, E., Nonomura, N., Takahara, S., & Okuyama, A. (2008). Carbamylated erythropoietin improves angiogenesis and protects the kidneys from ischemia-reperfusion injury. Cell transplantation, 17(1-2), 135–141. https://doi.org/10.3727/000000008783907044
    37. Tahora, S., Islam, M. M., Jahan, F., Rahman, A. K. M. S., Akbar, A. A. G., Mekhola, M. H., ... & Rahman, M. M. (2021). Carbamylated Haemoglobin is an Early Biomarker to Predict Chronic Kidney Disease. Archives of Nephrology and Urology, 4(3), 101-114. DOI: 10.26502/anu.2644-2833041
    38. Abdelwhab, S., & Ahmed, H. (2008). Carbamylated Hemoglobin as an Indicator of Hemodialysis adequacy and complications. Kidney, 17, 178-184. https://doi.org/10.1007/s00596-008-0037-2
    39. Keshava, H. K., Sultana, S., Suhas, G. C., & Chadrashekhar, H. R. (2024). A clinical comparative study on carbamylated haemoglobin as a surrogate marker to differentiate acute kidney injury from chronic kidney disease. Journal of Family Medicine and Primary Care, 13(9), 3995-4000. DOI: 10.4103/jfmpc.jfmpc_527_24
    40. Naresh, Y., Srinivas, N., Vinapamula, K. S., Pullaiah, P., Rao, P. V. L. N. S., & Sivakumar, V. (2018). Carbamylated Hemoglobin can Differentiate Acute Kidney Injury from Chronic Kidney Disease. Indian journal of nephrology, 28(3), 187–190. https://doi.org/10.4103/ijn.IJN_341_16
    41. Frazao, J. M., Barth, R. H., & Berlyne, G. M. (1995). Carbamylated hemoglobin in prerenal azotemia. Nephron, 71(2), 153–155. https://doi.org/10.1159/000188704
    42. Kellum, J. A., Romagnani, P., Ashuntantang, G., Ronco, C., Zarbock, A., & Anders, H. J. (2021). Acute kidney injury. Nature reviews. Disease primers, 7(1), 52. https://doi.org/10.1038/s41572-021-00284-z
    43. Vaidya SR, Aeddula NR. Chronic Kidney Disease. [Updated 2024 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535404/
    44. Evans, P. D., & Taal, M. W. (2015). Epidemiology and causes of chronic kidney disease. Medicine, 43(8), 450-453. https://doi.org/10.1016/j.mpmed.2015.05.005
    45. Almutary, H., Bonner, A., & Douglas, C. (2013). Symptom burden in chronic kidney disease: a review of recent literature. Journal of renal care, 39(3), 140–150. https://doi.org/10.1111/j.1755-6686.2013.12022.x
    46. Waikar, S. S., Betensky, R. A., & Bonventre, J. V. (2009). Creatinine as the gold standard for kidney injury biomarker studies?. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 24(11), 3263–3265. https://doi.org/10.1093/ndt/gfp428
    47. Al-Hazmi, S. F., Gad, H. G. M., Alamoudi, A. A., Eldakhakhny, B. M., Binmahfooz, S. K., & Alhozali, A. M. (2020). Evaluation of early biomarkers of renal dysfunction in diabetic patients. Saudi medical journal, 41(7), 690–697. https://doi.org/10.15537/smj.2020.7.25168
    48. van Deventer, H. E., Paiker, J. E., Katz, I. J., & George, J. A. (2011). A comparison of cystatin C- and creatinine-based prediction equations for the estimation of glomerular filtration rate in black South Africans. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 26(5), 1553–1558. https://doi.org/10.1093/ndt/gfq621
    49. Soveri, I., Berg, U. B., Björk, J., Elinder, C. G., Grubb, A., Mejare, I., Sterner, G., Bäck, S. E., & SBU GFR Review Group (2014). Measuring GFR: a systematic review. American journal of kidney diseases : the official journal of the National Kidney Foundation, 64(3), 411–424. https://doi.org/10.1053/j.ajkd.2014.04.010
    50. Florkowski, C. M., & Chew-Harris, J. S. (2011). Methods of Estimating GFR - Different Equations Including CKD-EPI. The Clinical biochemist. Reviews, 32(2), 75–79.
    51. Bonventre, J. V., & Yang, L. (2010). Kidney injury molecule-1. Current opinion in critical care, 16(6), 556–561. https://doi.org/10.1097/MCC.0b013e32834008d3
    52. Bolignano, D., Donato, V., Coppolino, G., Campo, S., Buemi, A., Lacquaniti, A., & Buemi, M. (2008). Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. American journal of kidney diseases : the official journal of the National Kidney Foundation, 52(3), 595–605. https://doi.org/10.1053/j.ajkd.2008.01.020
    53. Devarajan P. (2008). Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease. Scandinavian journal of clinical and laboratory investigation. Supplementum, 241, 89–94. https://doi.org/10.1080/00365510802150158
    54. Bethea, M., & Forman, D. T. (1990). Beta 2-microglobulin: its significance and clinical usefulness. Annals of clinical and laboratory science, 20(3), 163–168.
    55. Miyata, T., Jadoul, M., Kurokawa, K., & Van Ypersele de Strihou, C. (1998). Beta-2 microglobulin in renal disease. Journal of the American Society of Nephrology : JASN, 9(9), 1723–1735. https://doi.org/10.1681/ASN.V991723
    56. Langston C. (2008). Managing fluid and electrolyte disorders in renal failure. The Veterinary clinics of North America. Small animal practice, 38(3), 677–xiii. https://doi.org/10.1016/j.cvsm.2008.01.007
    57. Dhondup, T., & Qian, Q. (2017). Electrolyte and Acid-Base Disorders in Chronic Kidney Disease and End-Stage Kidney Failure. Blood purification, 43(1-3), 179–188. https://doi.org/10.1159/000452725
    58. Mashahit, M. A. H., El-Shafeey, S. M., El-Toukhy, H. S., & Ali, R. A. (2023). Ability of carbamylated hemoglobin to predict duration and stage of renal diseases. Fayoum University Medical Journal, 11(3), 81-90. fumj.journals.ekb.eg

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Chakraborty, A., Dhok, A., Anjankar, A., Vagga, A., & jha, R. (2025). Carbamylated haemoglobin as a marker for predicting progression of renal failure. Multidisciplinary Reviews, 8(7), 2025217. https://doi.org/10.31893/multirev.2025217
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