Hyperuricemia, Urate Lowering Therapy and Kidney Function: A Systemic Review and Meta-Analysis

Gaurav Sharma¹, Abhishek Dubey¹ and Jasvinder A. Singh², ¹Internal Medicine, Seth GS Medical College and KEM Hospital, Mumbai, India, ²University of Alabama at Birmingham, Birmingham, AL

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: hyperuricemia and renal disease

Session Information

Date: Sunday, November 8, 2015

Title: Metabolic and Crystal Arthropathies Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: To determine whether hyperuricemia is associated with deterioration of kidney function and to examine whether urate-lowering therapies (ULTs) can improve or maintain kidney function.

Methods: A literature search of various databases was performed. All randomized control trials, controlled clinical trials and observational studies of interest were included. Protocol was registered in PROSPERO database. Duplicate, independent screening of titles and abstracts and data abstraction was done . The primary outcome was renal function (measured by serum creatinine level, changes in GFR, Cystatin C level, progression to chronic kidney disease or end stage renal disease). Meta-analysis for association between increased serum uric acid and renal function (Q1) and for effect of urate lowering therapy on renal function(Q2) was done using RevMan 5.3.

Results: 5817 abstract and titles were screened for uric acid and renal outcomes (Q1) and for urate-lowering therapy and renal outcomes (Q2) questions. 24 studies with 316,391 patients and 5 studies with 522 patients qualified for final analyses, respectively. Mean ages were 20-79 years (Q1) and 35-85 years (Q2). Mean follow-up was 2 to 10 year and 2 months to 2 years, respectively.

We found that individuals with hyperuricemia (defined as serum uric acid ≥ 7 mg/dL in men and ≥ 6 mg/dL in women) had 1.5 times greater odds each of decline of glomerular filtration rate (GFR) by ≥ 3 mL/min/1.73 m²/year or development of new albuminuria [defined as development of either micro albuminuria :Urine Albumin to Creatinine Ratio(UACR) is 30-300 mg/g or overt proteinuria (UACR > 300 mg/g)] compare to individuals with normal serum uric acid level. Individuals with hyperuricemia developed chronic kidney disease (CKD) about 2 times more frequently than the normourcemic individuals (Table 1).

For Q2, we found 3 studies of Allopurinol (272 patients), 1 for Rasburicase (38 patients) and 1 for Pegloticase (212 patients). Compared to placebo patients treated with standard ULT doses had better glomerular filtration, creatinine clearance and low levels of serum Creatinine and serum Cystatin C (Table 2);urine albumin did not differ significantly.

Conclusion: Our systemic review and meta-analysis revealed an important relationship between hyperuricemia and renal function deterioration/renal failure development. Evidence is emerging that ULT use may improve renal function, although more data are needed. These findings indicate that appropriate treatment of hyperuricemia in patients with gout or other hyperuricemic condition may help to preserve kidney function.

Table 1: Comparison of renal functions in Hyperuricemic (serum uric acid ≥ 7 mg/dL in men and ≥ 6 mg/dL in wome) vs Normouricemic group of individuals.
Outcome	Odds Ratio [95% CI]	Hazard Ratio [95% CI]	Quality of evidence (Newcastle-Ottawa scale)
Decline in Glomerular Filtration Rate(decline of eGFR ≥ 3mL/min/1.73m2)	1.48 [1.19, 1.83]	——	Moderate
Albuminuria (defined as both microalbuminuria [Urine Albumin to Creatinine Ratio (UACR) >/= 30 mg/g) and overt is >/= 300 mg/g]	1.55 [1.16, 2.07]	——	Moderate
Chronic Kidney Disease (GFR </= 60 mL/min/1.73 m2)	1.12 [1.06, 1.18]	1.96 [1.43, 2.70]	Moderate-high
End Stage Renal Disease (defined as requirement of dialysis or renal transplant)	——	1.12 [0.97, 1.30]	Moderate

Table 2: Comparison of effect Urate-lowering Therapy (ULT) vs Placebo on renal functions.
Number of Studies per outcome	Number of patients per outcome	Outcome	Mean Difference [95 % CI]	Quality of evidence [using Cochrane risk of bias Assessment tool]
2	218	Glomerular Filtration Rate (mL/min/1.73 m2) **Normal value is ≥ 90 mL/min/1.73 m²	5.98 [2.09, 9.87]	High Quality
2	167	Albuminuria (g/day) **Normal is value is excretion of <0.3 g/day	-0.03 [-0.10, 0.03]	Moderate -high
2	92	Serum Creatinine (mg/dL) **Normal range Men: 0.7-1.2 mg/dL Women: 0.6-1.1 mg/dL	-0.76 [-1.11, -0.40]	Moderate
1	38	Creatinine Clearance (mL/min) **Normal range Men: 97-137 mL/min Women: 88-128 mL/min	9.70 [3.18, 16.22]	Moderate
1	113	Serum Cystatin C (mg/L) **Normal range varies, depending on age and sex.	-0.50 [-0.78, -0.22]	High Quality

Disclosure: G. Sharma, None; A. Dubey, None; J. A. Singh, Takeda, Savient, 2,Takeda, Savient, merz, Regeneron, Allergan, Crealta, Bioiberica, 5.

To cite this abstract in AMA style:

Sharma G, Dubey A, Singh JA. Hyperuricemia, Urate Lowering Therapy and Kidney Function: A Systemic Review and Meta-Analysis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/hyperuricemia-urate-lowering-therapy-and-kidney-function-a-systemic-review-and-meta-analysis/. Accessed .

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