Asymptomatic hyperuricemia following renal transplantation

Table 1 Studies investigating the association between serum uric acid and renal function/graft survival in patients with kidney transplantation

Author	Numerosity	Average follow-up	Major findings	Ref.
Gerhardt et al (1999)	375	5 yr	Hyperuricemia (> 8.0 mg/dL in men and > 6.2 mg/dL in women), associated with reduced graft survival	[12]
Armstrong et al (2005)	90	2.2 yr	UA independent predictor of follow-up eGFR, but not of eGFR change over time	[13]
Akgul et al (2007)	133	3 yr	No association found between serum UA and the development of chronic allograft nephropathy	[14]
Saglam et al (2008)	34	Not reported	Serum UA associated to development of cyclosporine A nephropathy (biopsy proven)	[15]
Akalin et al (2008)	307	4.3 yr	Hyperuricemia 6 mo after transplantation significantly associated with new cardiovascular events and graft dysfunction	[16]
Bandukwala et al (2009)	405	2 yr	Hyperuricemia associated with cardiovascular events, and, inversely with eGFR	[17]
Meyer-Kriesche et al (2009)	1645	3 yr	UA levels one month after transplantation not associated with follow-up eGFR, after adjustment for baseline renal function	[20]
Karbowska et al (2009)	78	Not reported	Hyperuricemia associated with markers of endothelial dysfunction and inflammation	[19]
Min et al (2009)	368	58 ± 23 mo	Early-onset moderate-to-severe hyperuricaemia (serum UA ≥ 8.0 mg/dL) was found to be a significant risk factor for chronic allograft nephropathy (P = 0.035) and a poorer graft survival (P = 0.026) by multivariate analysis, whereas mild hyperuricaemia was not	[18]
Haririan et al (2010)	212	68 ± 27 mo	Serum UA during the first 6 mo postransplant, is an independent predictor of graft survival	[21]
Kim et al (2010)	356	102.6 ± 27.2 mo	Patients with eGFR> 60 mL/min per 1.73 m2. Hyperuricemia associated with decreased eGFR	[10]
Boratyńska et al (2010)	100	34 ± 12 mo	Serum UA not associated to graft survival during 30 mo of follow-up	[22]
Chung et al (2011)	351	10 yr	Hyperuricemia increased risk of cardiovascular complication; graft survival at 5 and 10 yr lower in hyperuricemic vs normouricemic patients (89% vs 96% and 81% vs 93% respectively, P = 0.02)	[23]
Kim et al (2011)	556	Not reported	Serum UA levels affect graft function, even after adjustment for baseline eGFR	[24]
Wang et al (2011)	524	10 yr	Retrospective study: UA significantly lower in patients with longer graft survival	[25]
Park et al (2013)	428	120 ± 58 mo	Serum UA associated with allograft loss, but rate of eGFR decline more potent predictor	[26]
Choi et al (2013)	378	10 yr	Graft survival (living donor renal transplantation) 88.6% in normouricemic vs 78.8% in hyperuricemic patients	[27]
Dahle et al (2014)	2200	7.4 yr	Highest serum UA quintile independently associated with increased HR (2.87, 95%CI: 1.55-5.32) of cardiovascular and all-cause (1.55, 95%CI: 1.09-2.25) mortality	[28]
Hart et al (2014)	149	5 yr	Post-hoc study of the ABCAN trial. Serum UA independently associated with increased odds of composite outcome of doubling of interstitium or ESRD from Interstitial Fibrosis/Tubular Atrophy, after adjusting for eGFR	[29]
Weng et al (2014)	880	43.3 ± 26.3 mo	Hyperuricemia associated with poorer graft survival (60.5% vs 75.8%, P = 0.007), no difference in all-cause mortality	[30]
Boratyńska et al (2014)	637	10 yr	Retrospective study. Hyperuricemia associated with chronic allograft dysfunction	[31]
Weng et al (2014)	124	14.3 mo	Patients undergoing biopsies for acute allograft dysfunction. Hyperuricemia associated with a greater cumulative incidence at one year of doubling serum creatinine or graft loss (29.8% vs 14.9%, P = 0.02) compared to normouricemia	[32]

UA: Uric acid; eGFR: Estimated glomerular filtration rate.

Table 2 Studies of uric-acid-lowering therapy in renal allograft recipients

Ref.	Study population	Average follow-up	Intervention/outcome(s)	Main study findings
Perez-Ruiz et al[34]	279 renal allograft recipients with hyperuricemia	38.6 ± 18.4 mo	Allopurinol, benziodarone/ serum UA levels	Both drugs effective in lowering serum UA; benziodarone safer in patients on azathioprine
Numakura et al[11]	121 renal allograft recipients with and without hyperuricemia	Up to 10 yr, mean not reported	Allopurinol/eGFR, graft survival	Hyperuricemia associated with reduced eGFR, but graft survival similar in normo and hyperuricemic patients
Osadchuck et al[35]	108 renal allograft recipients (54 patients treated vs 54 controls)	2 yr	Allopurinol/Serum UA levels, eGFR, graft survival	Reduced serum UA, preservation of eGFR in allopurinol treated patients; no differences in graft survival and blood pressure
Sofue et al[36]	93 renal allograft recipients (42 normouricemic, 51 hyperuricemic, 26 treated, 25 not treated)	1 yr	Febuxostat/serum UA levels, eGFR	Serum UA lower and eGFR stable in patients treated with febuxostat
Tojimbara et al[38]	23 renal allograft recipients with hyperuricemia	12 ± 2 mo	Febuxostat/serum UA, eGFR	Serum UA lower after treatment with febuxostat; eGFR stable

UA: Uric acid; eGFR: Estimated glomerular filtration rate.