Association between serum uric acid and renal outcome in patients with biopsy-confirmed diabetic nephropathy

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Abstract

Objective

To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN).

Methods

A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 μmol/L ( n = 98); Q2 group: 358.23 ± 14.03 μmol/L ( n = 99); Q3 group: 405.50 ± 14.59 μmol/L ( n = 98) and Q4 group: 499.14 ± 56.97μmol/L ( n = 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan–Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes.

Results

During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN ( P = 0.747) was shown in the Kaplan–Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621–2.992; P = 0.439), 1.518 (0.768–3.002; P = 0.230) and 1.411 (0.706–2.821; P = 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 ( P = 0.652).

Conclusions

No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.

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Most cited references 25

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Pathologic classification of diabetic nephropathy.

Thijs W Cohen Tervaert, Antien Mooyaart, Kerstin Amann … (2010)

Although pathologic classifications exist for several renal diseases, including IgA nephropathy, focal segmental glomerulosclerosis, and lupus nephritis, a uniform classification for diabetic nephropathy is lacking. Our aim, commissioned by the Research Committee of the Renal Pathology Society, was to develop a consensus classification combining type1 and type 2 diabetic nephropathies. Such a classification should discriminate lesions by various degrees of severity that would be easy to use internationally in clinical practice. We divide diabetic nephropathy into four hierarchical glomerular lesions with a separate evaluation for degrees of interstitial and vascular involvement. Biopsies diagnosed as diabetic nephropathy are classified as follows: Class I, glomerular basement membrane thickening: isolated glomerular basement membrane thickening and only mild, nonspecific changes by light microscopy that do not meet the criteria of classes II through IV. Class II, mesangial expansion, mild (IIa) or severe (IIb): glomeruli classified as mild or severe mesangial expansion but without nodular sclerosis (Kimmelstiel-Wilson lesions) or global glomerulosclerosis in more than 50% of glomeruli. Class III, nodular sclerosis (Kimmelstiel-Wilson lesions): at least one glomerulus with nodular increase in mesangial matrix (Kimmelstiel-Wilson) without changes described in class IV. Class IV, advanced diabetic glomerulosclerosis: more than 50% global glomerulosclerosis with other clinical or pathologic evidence that sclerosis is attributable to diabetic nephropathy. A good interobserver reproducibility for the four classes of DN was shown (intraclass correlation coefficient = 0.84) in a test of this classification.

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Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

E Schwiers, P HOCHSTEIN, R Cathcart … (1981)

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Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level.

Yui-Pong Siu, Kay-Tai Leung, Matthew Tong … (2006)

Hyperuricemia is associated strongly with the development of hypertension, renal disease, and progression. Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase. We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients. We conducted a prospective, randomized, controlled trial of 54 hyperuricemic patients with chronic kidney disease. Patients were randomly assigned to treatment with allopurinol, 100 to 300 mg/d, or to continue the usual therapy for 12 months. Clinical, hematologic, and biochemical parameters were measured at baseline and 3, 6, and 12 months of treatment. We define our study end points as: (1) stable kidney function with less than 40% increase in serum creatinine level, (2) impaired renal function with creatinine level increase greater than 40% of baseline value, (3) initiation of dialysis therapy, and (4) death. One patient in the treatment group dropped out because of skin allergy to allopurinol. Serum uric acid levels were significantly decreased in subjects treated with allopurinol, from 9.75 +/- 1.18 mg/dL (0.58 +/- 0.07 mmol/L) to 5.88 +/- 1.01 mg/dL (0.35 +/- 0.06 mmol/L; P < 0.001). There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups. There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy, although it did not reach statistical significance (P = 0.08). Overall, 4 of 25 patients (16%) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients (46.1%) in the control group (P = 0.015). Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease. Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls. Results of this study need to be confirmed with an additional prospective trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease subpopulations.

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Author and article information

Journal

Journal ID (nlm-ta): Endocr Connect

Journal ID (iso-abbrev): Endocr Connect

Journal ID (hwp): EC

Title: Endocrine Connections

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Electronic): 2049-3614

Publication date (Electronic): 15 September 2021

Publication date Collection: 01 October 2021

Volume: 10

Issue: 10

Pages: 1299-1306

Affiliations

[1 ]Division of Nephrology , West China Hospital of Sichuan University, Chengdu, Sichuan, China

[2 ]Laboratory of Diabetic Kidney Disease , Centre of Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, Sichuan, China

[3 ]Division of Pathology , West China Hospital of Sichuan University, Chengdu, Sichuan, China

[4 ]Department of Diabetes , Central Clinical School, Monash University, Melbourne, Australia

[5 ]Division of Endocrinology , West China Hospital of Sichuan University, Chengdu, Sichuan, China

[6 ]Centre of Diabetes and Metabolism Research , West China Hospital of Sichuan University, Chengdu, Sichuan, China

Author notes

Correspondence should be addressed to F Liu: liufangfh@ 123456163.com

Author information

Fang Liu http://orcid.org/0000-0003-1121-3004

Article

Publisher ID: EC-21-0307

DOI: 10.1530/EC-21-0307

PMC ID: 8558902

PubMed ID: 34524970

SO-VID: 370c40f9-5321-416a-b200-b558e96d7736

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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Association between serum uric acid and renal outcome in patients with biopsy-confirmed diabetic nephropathy

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Abstract

Objective

Methods

Results

Conclusions

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Society for Endocrinology

Most cited references 25

Pathologic classification of diabetic nephropathy.

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level.

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