Uric acid handling in autosomal dominant polycystic kidney disease with normal filtration rates

doi:10.1016/0002-9343(90)90097-W

The American Journal of Medicine

Volume 89, Issue 1, July 1990, Pages 49-52

https://doi.org/10.1016/0002-9343(90)90097-W Get rights and content

Abstract

purpose: Patients with autosomal dominant polycystic kidney disease (ADPKD) are alleged to have more frequent or more pronounced alterations of uric acid homeostasis than are seen in most other types of chronic renal diseases. We performed this study to examine the hypothesis that individuals with ADPKD have abnormal uric acid homeostasis that is manifest before the development of renal insufficiency.

patients and methods: We studied 301 subjects, 163 with ADPKD and 138 relatives without ADPKD (NADPKD), by ultrasonography. The subjects were interviewed and examined. Venous blood and two 24-hour urine collections were obtained for uric acid and creatinine determinations.

results: Presence of hyperuricemia, serum uric acid levels, uric acid clearance, and fractional excretion of uric acid did not differ between ADPKD and NADPKD subjects with normal renal function (creatinine clearance greater than 80 mL/minute/1.73 m²). Clearance of uric acid decreased and fractional excretion increased in subjects with decreased renal function in both groups. Female gender enhanced renal excretion of uric acid in both groups and hypertension depressed it except in men with ADPKD, who had higher fractional excretions for uric acid than did hypertensive NADPKD men.

conclusions: Uric acid homeostasis is preserved in individuals with ADPKD with normal renal function when compared to unaffected family members. Hyperuricemia and decreased renal excretion of uric acid develop as renal function worsens in ADPKD, similar to that in control subjects. The expected depressing effect of hypertension on renal handling of uric acid was not seen in men with ADPKD, speculatively due to an effect of atrial natriuretic factor.

References (25)

TH Steele et al.
The renal mechanism for urate homeostasis in normal man
Am J Med
(1967)
E Mejias et al.
Hyperuricemia, gout, and autosomal dominant polycystic kidney disease
Am J Med Sci
(1989)
TH Steele et al.
The contribution of residual nephrons within the chronically diseased kidney to urate homeostasis in man
Am J Med
(1967)
PA Gabow et al.
The clinical utility of renal concentrating capacity in polycystic kidney disease
Kidney Int
(1989)
F Coe
Hyperuricosuric calcium oxalate nephrolithiasis
Kidney Int
(1978)
PE Bell et al.
Hypertension in autosomal dominant polycystic kidney disease
Kidney Int
(1988)
JJ Grantham
Polycystic kidney disease: a predominance of giant nephrons
Am J Physiol
(1983)
PD Wilson et al.
Alterations in membrane NaK-ATPase in adult human polycystic kidney disease (APKD)
Kidney Int
(1989)
JB Wyngaarden et al.
Gout and hyperuricemia
JJ Grantham et al.
Renal handling of organic anions and cations; metabolism and excretion of uric acid

WN Kelley et al.

Gout and other disorders of purine metabolism

BT Emmerson

Hyperuricemia, gout, and the kidney

Cited by (22)

Anatomic and metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease
2000, American Journal of Kidney Diseases
The prevalence of nephrolithiasis is considerably greater in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. We evaluated anatomic and metabolic factors that may be associated with an increased prevalence of nephrolithiasis in patients with ADPKD. We compared anatomic parameters among ADPKD patients with or without nephrolithiasis as diagnosed by ultrasonography, whereas metabolic factors were determined by 24-hour urinary chemical analysis. Patients with ADPKD and nephrolithiasis had more renal cysts (P < 0.05) and a larger predominant renal cyst size (P < 0.005) than patients without nephrolithiasis. Concurrently, individual stone-forming kidneys had a greater cyst number (P < 0.05) and a significantly larger predominant cyst size (P < 0.01) compared with kidneys without stones. Patients with ADPKD and nephrolithiasis had a significantly lower creatinine clearance than those without nephrolithiasis (68.7 ± 8.6 versus 94.8 ± 5.4 mL/min, respectively; P < 0.05). Twenty-four–hour urinary analysis showed that patients with ADPKD and nephrolithiasis had significantly lower urinary volumes (P < 0.05), and levels of urinary phosphate (P < 0.05), magnesium (P < 0.005), and potassium (P < 0.05). Although not statistically significant, patients with ADPKD with stones tended to have lower levels of urinary citrate, and both groups showed a high percentage (range, 49% to 60%) of patients with hypocitraturia. Our data are consistent with the hypothesis that patients with ADPKD who develop nephrolithiasis do so because of increased intrarenal anatomic obstruction, as well as lower levels of such urinary inhibitors of stones as magnesium and citrate.
Polycystic renal disease
1993, Urology
Autosomal Dominant Polycystic Kidney Disease—More Than a Renal Disease
1990, American Journal of Kidney Diseases
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease, affecting a half million Americans. The clinical phenotype can result from at least two different gene defects. One gene that can cause ADPKD has been located on the short arm of chromosome 16. This discovery has made possible new methods for diagnosing the disorder in gene carriers prior to the development of renal cysts. Although renal cysts are clearly an important manifestation of the gene defect, other systemic manifestations are both common and clinically important. Cardiac valvular lesions, intracranial aneurysms, hepatic cysts, and diverticula are included in the array of systemic manifestations. Moreover, renal cysts are only one of a myriad of renal manifestations. Although ADPKD was long considered an adult cystic disease, it is also a common cause of childhood cystic disease and must be considered in the differential diagnosis in that setting.
Hypocitraturia is present when renal function is impaired in diverse nephropathies and is not related with serum bicarbonate levels
2022, International Urology and Nephrology
Alterations of proximal tubular secretion in autosomal dominant polycystic kidney disease
2020, Clinical Journal of the American Society of Nephrology
Nephrolithiasis in polycystic kidney disease: Risk factors, treatment and prevention
2015, Nephrolithiasis: Risk Factors, Treatment and Prevention

View all citing articles on Scopus

^☆: This work was performed at the University of Colorado Health Sciences Center and was supported by Grant 5 P01 DK34039 from the Department of Health and Human Services, Public Health Service. National Institute of Diabetes and Digestive and Kidney Diseases, and by Grant RR-00051 from the General Clinical Research Centers Research Program of the Division of Research Resources, National Institutes of Health, Bethesda, Maryland.

^☆☆: These data were presented in part at the American Society of Nephrology meeting in December 1987, and were published in the program of the 20th Annual Meeting of the American Society of Nephrology, 1987, page 67a, in abstract form.

View full text

Uric acid handling in autosomal dominant polycystic kidney disease with normal filtration rates☆,☆☆

Abstract

Am J Med

Am J Med Sci

Am J Med

Kidney Int

Kidney Int

Kidney Int

Polycystic kidney disease: a predominance of giant nephrons

Am J Physiol

Alterations in membrane NaK-ATPase in adult human polycystic kidney disease (APKD)

Kidney Int

Gout and hyperuricemia

Renal handling of organic anions and cations; metabolism and excretion of uric acid

Gout and other disorders of purine metabolism

Hyperuricemia, gout, and the kidney