URATE HOMEOSTASIS IN POLYCYSTIC KIDNEY DISEASE: COMPARISON WITH CHRONIC GLOMERULONEPHRITIC KIDNEY

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) might affect urate homeostasis and clearance. Renal tubular urate transport was studied by means of probenecid (PB) and pyrazinamide (PZA) tests in individuals with ADPKD and normal renal function as well as various degrees of renal failure (49 patients). Comparisons were made between polycystic and chronic glomerulonephritic kidney (CGNK), as well as with controls (men with normal renal function). Patients with ADPKD and normal renal function showed plasma urate levels within normal range and normal renal urate handling. In contrast higher plasma urate levels comparing to controls were found in patients with CGNK and normal renal function. During the evolution of renal failure ADPKD patients showed lower urate plasma levels and higher renal clearance as well as, fractional urate excretion, comparing to CGNK patients with the same degree of renal failure. In conclusion patients with ADPKD and normal renal function have normal urate handling and plasma urate levels within normal range. With increasing severity of disease and during evolution of renal failure CGNK patients showed higher urate plasma levels and lower clearances comparing to ADPKD patients. When renal disease becomes more advanced there was no difference in renal urate handling between ADPKD and CGNK patients.

• Adult dominant polycystic kidney disease
• Glomerulonephritis
• Chronic renal failure
• Renal urate handling
• Urate homeostasis
• Hyperuricemia

INTRODUCTION

Autosomal dominant polycystic kidney disease (ADPKD) alters tubular membrane transport process[[1]], [[2]] and might affect renal urate handling and homeostasis of urate. The renal mechanisms for urate transport in man include glomerular filtration, almost complete (99%) presecretory reabsorption, tubular secretion and postsecretory reabsorption (four component hypothesis).[[3]], [[4]] Data concerning a relationship between altered urate homeostasis and ADPKD are scarce and conflicting.[[5]], [[6]], [[7]], [[8]], [[9]] Recently, preserved urate homeostasis in individuals with ADPKD before the development of renal insufficiency has been reported and hyperuricemia with decreased renal urate excretion developed as a result of renal function deterioration.[[10]] However hyperuricemia due to diminished renal secretory component in ADPKD patients has also been reported.[[11]] Studies concerning renal tubular urate transport mechanisms in polycystic kidneys with normal and impaired renal function are lacking in the literature.

Therefore, we performed the present study to examine tubular urate transport by means of probenecid (PB) and pyrazinamide (PZA) tests in individuals with ADPKD and normal renal function as well as various degrees of renal insufficiency. Comparisons were made between polycystic and chronic glomerulonephritic kidneys (CGNK) with similar creatinine clearance (Ccr). The response of urate excretion to PB and PZA has been widely used to analyze the tubular mechanisms of urate transport in normal subjects as well as in patients with renal failure or abnormal urate clearance.[[12]], [[13]]

PATIENTS AND METHODS

Eighty-five patients (49 with ADPKD and 36 with CGNK) and 19 control subjects were studied. Patients with ADPKD and CGNK were divided into groups according to their creatinine clearance (Ccr). Group A consisted of 32 individuals (13 males, 19 females) with Ccr > 80 mL/min/1.73 m² body area. Among those 22 (7 males, 15 females (3 of them had menopause)) had ADPKD and 10 (6 males, 4 females) CGNK. The control group consisted of 19 subjects (7 males, 12 females (2 of them had menopause)) with normal renal function.

Group B included 23 patients with Ccr = 20–80 mL/min/1.73 m² body area: 12 with ADPKD (8 male, 4 female) and 11 with CGNK (8 male, 3 female).

Group C included 30 patients with Ccr < 20 mL/min/1.73 m² body area: 15 with ADPKD (8 male, 7 female) and 15 with CGNK (8 male, 7 female).

All subjects underwent a detailed formalized interview including a complete history and physical examination. Patients with a family history of gout or any other disease known to affect urate excretion were excluded. Subjects with proteinuria more than 1 g/24 h, with a blood pressure higher than 150/90 mm Hg, undergoing dialysis or with renal transplants excluded, too. Diuretics or any other drugs affecting urate homeostasis were stopped at least 10 days before the tests (PZA and PB). All patients had more than 4 g/dL plasma albumin and their hematocrit were stable during tests period.

Complete abdominal ultrasonography or computer tomography (CT) was performed and subjects were classified as having ADPKD if many cysts present in both kidneys (usually without parenchyma between them), with a positive family history for the ADPKD. Sings other such as cysts in the liver more than 10, hematuria, hypertension, e.c.t help us in the diagnosis. Diagnosis of glomerulonephritis was histologically proved in 28 patients. In the rest 9 CGNK patients who belong to C group diagnosis was established from the ultrasonography results (small kidneys with enhancement of echogenicity, without scaring and with normal outline) and from the history. The study protocol had been approved by the medical ethics committee.

Glomerular filtration rate was calculated as endogenous creatinine clearance (mL/min/1.73 m² body area).

During the test's period all the patients followed their diet according their renal function (0.6–1.2 g proteins/kg.b.w.). All the subjects underwent the PB test that was followed by the PZA test after a minimum period of 7 days. The study started in the morning after an overnight fast; breakfast was omitted. PB and PZA tests were performed according to the protocols previously described. Standard clearance techniques were employed. In order to attain a urine flow rate of approximately 2–3 mL/min, the patients ingested 15 mL/kg.b.w tap water before and during each clearance study urinary losses were replaced. All urine specimens exceeded 100 mL in volume. Each test consisted of two phases; one before (control phase) and the other after administration (PB 2 g orally or PZA 3 g orally in a single dose). The control phase of each test involved two or three 45 min clearance periods of the same duration. Urine was collected for 4 additional clearance periods. The first clearance period after PZA administration started after a 60 min delay.

A venous blood sample was drown in the middle of each clearance period. Urate concentrations both in urine and plasma measured using a uricase method (Peridochrome, Boehringer Manheim, No. 575488). Urine and serum creatinine concentrations were determined enzymatically (determination of real creatinine, bio Merieux No. 61169, in combination with the reagent Lloyd, bio Merieux No. 61351).

The values for creatinine clearance, plasma urate clearance and the ratio of urate clearance to creatinine clearance as well as the values for filtered and excreted urate represent averages of the control clearance periods in PB and PZA tests. Patients with a deviation of more than 10% between any reciprocal measurement were excluded.

Statistical analysis was performed by unpaired student's t-test. A p value < 0.05 was considered significant.

CALCULATIONS

PZA-nonsuppressible urate = minimum value of urate excretion after PZA administration (this parameter represents a measure of filtered urate that escapes presecretory reabsorption).

Presecretory reabsorption = filtered urate i.e., (GFR × plasma urate) minus PZA-nonsuppressible urate.

Postsecretory reabsorption = maximum urate excretion after PB minus urate excretion in the control period (uricosuric response to PB).

PZA-suppressible urate = urate excretion in the control period minus PZA-nonsuppressible urate (this parameter represents a measure of “net secretion” i.e., the difference between secretion and postsecretory reabsorption).

Secreted urate = excreted urate + postsecretory reabsorption minus PZA-nonsuppressible urate, because excreted = (filtered-presecretory reabsorbed) + (secreted-postsecretory reabsorbed) and (filtered-presecretory reabsorbed) = PZA-nonsuppressible therefore, excreted = (PZA-nonsuppressible) + (secreted)−(postsecretory reabsorbed).

RESULTS

In group A patients with ADPKD creatinine clearance showed no difference (p = NS) compared with normal subjects and CGNK patients. Also, in group B and C patients' values of creatinine clearances did not differ significantly (p = NS) (Table 1).

Table 1.

		Ccr	Pur	Cur	Cur/Ccr (FEur)	Fur	Sur
GROUP A	Controls	108.4	0.25	9.37	0.087	4126	1228
	(n = 19)	±14.7	±0.06	±1.59	±0.020	±991	+ 298
	ADPKD	108.8	0.27	9.53	0.087	4406	1127
	(n = 22)	±14.5	±0.07	±2.73	0.025	±1121	±402
	CGNK	115.0	0.32	7.39	0.067	5226	1185
	(n = 10)	±28.2	±0.06	±1.59	0.021	±998	±274
	p Controls vs ADPKD	NS	NS	NS	NS	NS	NS
	p Controls vs CGNK	NS	<0.01	<0.01	<0.02	<0.01	NS
	p ADPKD vs CGNK	NS	NS	<0.05	<0.05	NS	NS
GROUP B	ADPKD	37.2	0.37	12.56	0.373	6217	1061
	(n = 12)	±12.9	±0.06	±4.22	±0.182	±1006	±287
	CGNK	44.1	0.44	8.16	0.217	7354	1625
	(n = 11)	±18.9	±0.08	±2.84	±0.105	±1481	±489
	p ADPKD vs CGNK	NS	<0.05	<0.01	<0.05	<0.05	<0.01
GROUP C	ADPKD	9.49	0.40	27.69	6.806	6586	1350
	(n = 15)	±5.87	±0.09	±15.39	±14.42	±1677	±1044
	CGNK	12.41	0.43	15.98	1.495	7212	1700
	(n = 15)	±3.87	±0.06	±5.84	±0.863	±1129	±614
	p ADPKD vs CGNK	NS	NS	<0.02	NS	NS	NS

Clearance creatinine (Ccr, mL/min), plasma urate (Pur, mmol/L), clearance urate (Cur, mL/min), Cur/Ccr ratio and filtered urate (Fur, mg/min/100 mL GFR) and secreted urate (Sur, mg/min/100 mL GFR) in control subjects and 3 groups of ADPKD and CGNK patients (mean ± SD).

Plasma urate concentrations were similar in controls and group A ADPKD patients, p = NS, but higher than controls in group A CGNK patients (p < 0.01). Plasma urate levels increased progressively as Ccr decreased in all patients. The difference between ADPKD and CGNK patients was statistically significant in group B, p < 0.05, (Table 1).

In group A patients fractional urate excretion (FEur) was not different between ADPKD and controls, whereas it was significantly lower in CGNK patients (Table 1). FEur showed an augmentation with the progression of the disease that was greater in ADPKD than in CGNK patients. The difference was statistically significant in group B patients (p < 0.05) but not in group C patients (p = NS) (Table 1).

Filtered urate was significantly higher in CGNK patients than in controls (group A) (5226 ± 998 µg/min/100 mL GFR vs. 4126 ± 991, p < 0.01) as well as in CGNK than in ADPKD patients of group B (7354 ± 1481 µg/min/100 mL GFR vs. 6217 ± 1006, p < 0.05). In group C patients the difference (7212 ± 1129 µg/min/100 mL GFR vs. 6586 ± 1677) was not significant (p = NS) (Table 1).

Excreted urate did not differ significantly between ADPKD and CGNK patients in group A. These values were similar to the control subjects (p = NS). As Ccr decreased excreted urate per nephron was augmented progressively (Table 2). This increase was greater in ADPKD patients (107% vs. 52%). Thus, in group B excreted urate per nephron was significantly higher (p < 0.01) in ADPKD than in CGNK patients. The difference remains significant also, in group C patients (p < 0.05) (Table 2).

Table 2.

					PZA-nonsupr			Pr. R (% Fur)
		Eur	PZA-supr	PZA-nonsupr	(%Fur)	(%Eur)	Po. R
GROUP A	Controls	381	331	50.9	1.33	14.14	1228	98.60
	(n = 19)	±89	±94	±25.2	±0.81	±8.66	±298	±0.81
	ADPKD	397	354	42.3	0.91	10.82	1127	98.90
	(n = 22)	±63	±65	±19.9	±0.43	±5.43	±402	±0.42
	CGNK	376	323	53.6	1.01	13.44	1185	98.90
	(n = 10)	±81	±54	±42.9	±0.75	±7.87	±274	±0.75
	p Controls vs. ADPKD	NS	NS	NS	NS	NS	NS	NS
	p Controls vs. CGNK	NS	NS	NS	NS	NS	NS	NS
	p ADPKD vs. CGNK	NS	NS	NS	NS	NS	NS	NS
GROUP B	ADPKD	824	554	275	4.49	32.17	1061	95.42
	(n = 12)	±254	±175	±153	±2.68	±12.36	±287	±2.68
	CGNK	572	448	126	1.73	21.51	1702	98.10
	(n = 11)	±144	±106	±60	±0.70	±7.26	±429	±0.70
	p ADPKD vs. CGNK	<0.05	NS	<0.01	<0.01	<0.05	<0.05	<0.01
GROUP C	ADPKD	1772	1045	727	11.35	42.88	1350	87.50
	(n = 15)	±897	±687	±338	5.51	±16.25	±1044	±6.60
	CGNK	1147	634	556	7.96	48.72	1700	91.90
	(n = 15)	±420	±276	±397	±5.83	±32.87	±614	±5.80
	p ADPKD vs. CGNK	<0.05	<0.05	NS	NS	NS	NS	NS

Concentrations of excreted urate (Eur), PZA-suppressible urate (PZA-supr), and PZA-non suppressible urate (PZA-non supr) in mg/min/100 mL GFR, PZA-non suppressible as percentage of filtered urate (% Fur) and as percentage of excreted urate (%Eur), uricosuric response to PB or postsecretory reabsorption (Po, R, mg/min/100 mL GFR) as well as presecretory reabsorption (Pr. R) as percentage of Fur in control subjects and in 3 groups of polycystic (ADPKD) and glomerulonephritic (CGNK) patients (means ± SD).

PZA-suppressible and PZA-nonsuppressible urate did not differ significantly in group A patients compared with controls (Table 2). In group B patients PZA-suppressible urate was increased compared with group A patients (ADPKD = 554 ± 175 µg/min/100 mL GFR vs. 354 ± 65, CGNK = 448 ± 106 µg/min/100 mL GFR vs. 323 ± 54) but there was not significantly difference between ADPKD and CGNK patients. In group C patients with ADPKD showed a significantly higher PZA-suppressible urate than CGNK patients, (p < 0.05). A significant increase was also observed in PZA-nonsuppressible urate excretion with the progression of renal failure. So the PZA-nonsuppressible urate was significantly higher (p < 0.01) in ADPKD patients (275 ± 153 µg/min/100 mL GFR vs. 126 ± 60) of group B (Table 2).

PZA-nonsuppressible urate expressed as percentage of filtered amount was similar in controls as well as in ADPKD and CGNK patients of group A. There was a progressive increase of the percentage of PZA-nonsuppressible urate in group B and C patients, but this was statistically higher only in ADPKD patients of group B (4.49 ± 2.68% vs. 1.73 ± 0.70%) (p < 0.01) (Table 2).

A similar change was also observed when PZA-nonsuppressible urate excretion expressed as percentage of excreted urate. This percentage showed a progressive increase and was statistically higher (p < 0.05) in group B ADPKD (32.17%) than in CGNK patients (21.51%) of the same group (Table 2).

Concerning uricosuric response to PB (postsecretory reabsorption) no difference between controls and group A patient was observed. Uricosuric response was significantly lower (p < 0.001) in ADPKD patients of group B (1061 ± 287 µg/min/100 mL GFR vs. 1702 ± 429) (Table 2).

Presecretory reabsorption of urate/100 mL GFR was almost complete in normal subjects (98.60% of filtered urate) as well as in group A patients (ADPKD = 98.90% and CGNK = 98.90%). As GFR decreased, presecretory urate reabsorption/100 mL GFR, expressed as percentage of filtered urate/100 mL GFR was reduced progressively. This reduction was higher in ADPKD patients of group B (p < 0.01). Difference between group C patients were not significant (p = NS) (Table 2).

DISCUSSION

This study of ADPKD with preserved renal function clearly demonstrates that urate metabolism is not altered by ADPKD. Indeed, plasma urate concentrations as well as urate clearance and fractional urate excretion appeared similar in control subjects and ADPKD patients with normal renal function. These findings are consistent with recently reported observations.[[10]] Moreover, patients with CGNK showed lower urate clearance and fractional urate excretion than patients with ADPKD and normal renal function. Also, CGNK patients showed increased plasma urate concentrations and decreased urate excretion compared with control subjects (Table 1).

The renal urate handling can be conveniently rationalized by a four-component sequential system: (1) filtration, (2) reabsorption of filtered, (3) tubular excretion, and (4) reabsorption of secreted urate. In fact the renal tubular urate transport is much more complex since bidirectional transport takes place.[[14]] The response of urate excretion to drugs that alter renal tubular of urate has been used to analyze the tubular mechanisms of urate transport in man by several authors.[[3]], [[4]], [[12]], [[14]], [[15]], [[16]], [[17]], [[18]], [[19]], [[20]], [[21]], [[22]], [[23]] However, secretion and reabsorption may occur in the same tubular segments, and may have active and passive components. Reabsorption of filtered and secreted urate may occur at the same or separate sites and by the same or distinct mechanisms. Thus, urate transport in man may be more complex than present techniques can analyze and interpretations should be considered to allow only tentative classification as to the most likely defect.[[15]]

Pyrazinamide is rapidly metabolized in man to pyrazinoic acid (PZA), a potent inhibitor of urate excretion. In 1967, Steele and Rieselbach demonstrated that in normal subjects oral administration of 3 g of PZA reduced the renal excretion to less than 2% of the filtered load. This effect persisted over a wide range of serum urate concentrations and filtered urate loads.[[3]] These results along with those from micropuncture studies in animals indicate that PZA profoundly inhibits urate secretion. Partial inhibition of urate reabsorption is observed at high concentrations of PZA. However, since these high concentrations may not be achieved following oral PZA in man, the PZA effect has generally been considered to approximate nearly complete inhibition of urate secretion without significant effect on urate reabsorption.[[15]], [[24]]

Studies of the effect of inhibition of urate reabsorption have most often utilised PB. Uricosuric response is calculated as the increase in urate excretion from the mean of the control collections.[[15]], [[25]]

Standard interpretation of results is based upon the assumption that urate is freely filtered at the glomeruli, that under the conditions of these studies PZA inhibits urate secretion completely or nearly completely and does not affect reabsorption, and that the uricosuric drug does not inhibit secretion. While neither of these statements is likely to be completely true, they may provide reasonable approximation.[[15]]

Results from PZA and PB studies showed no any difference between control subjects and ADPKD as well as CGNK patients with normal renal function (Table 2). Namely, presecretory reabsorption was nearly complete and amounted about 99% of the filtered urate load in all three groups (Table 2). Also, PZA suppressible and PZA-nonsuppressible urate values did not differ significantly between normal subjects and ADPKD as well as between CGNK and ADPKD patients (Table 2). However, Cur as well as FEur was significantly higher in ADPKD compared with CGNK patients of group A. A possible explanation is that mechanisms responsible for differences in urate clearance and fractional urate excretion may be more refined than the present techniques can analyze.

As anticipated, with increasing severity of chronic renal failure, plasma urate levels rise progressively and as glomerular filtration rate decreases, fractional urate excretion increases (Table 1). There is a marked increase in the urate excretion per nephron as the renal function deteriorates (Table1). However, until creatinine clearance had decreased to 20 mL/min, the renal urate handling appeared to be different in ADPKD subjects as compared to the glomerulonephritic patients with the same degree of renal failure (Group B). Indeed, ADPKD patients with a mean value of creatinine clearance very close to those of CGNK subjects showed a significantly higher urate clearance and fractional urate excretion. As a consequent, plasma urate concentrations were significantly lower in ADPKD than in CGNK patients. As renal failure becomes more severe, i.e., less than 20 mL/min (Group C) fractional urate clearance continues to increase, but differences between the two groups of uremic patients become less apparent (Table 1). Thus, in advanced renal disease renal urate handling appeared to be similar in the two groups.

The increased urate excretion per nephron in chronic renal failure might be attributed either to an augmented urate secretion or to a diminished pre- or postsecretory reabsorption. Also, a combination of both factors cannot be ruled out. In normal subjects, the PZA-nonsuppressible urate per nephron, i.e., the amount of filtered urate that escapes reabsorption, was 1.33% of the filtered load, suggesting an almost complete reabsorption (98.60%) (Table 2). With increasing severity of disease, the presecretory urate reabsorption per nephron, expressed as a percentage of filtered urate, showed a diminution that was greater in ADPKD than in CGNK patients. Thus, when Clur ranged among 20–80 mL/min, patients with ADPKD reabsorbed 95.42% of the filtered amount while, CGNK patients reabsorbed a percentage of 98.10% (p<0.01). Our findings from ADPKD were comparable to those reported by Garyfallos et al. in a study concerning uremic patients of various etiology.[[12]] It seems likely that CGNK patients reabsorb a component of filtered amount major than ADPKD patients with the same degree of renal failure.

The PZA test has already been used in uremic patients.[[12]], [[13]], [[26]] Steele and Rieselbach[[13]] observed a similar suppressive effect on urate secretion after oral or intravenous administration of pyrazinamide. Consequently, a possible ineffective absorption of pyrazinamide from the gastrointestinal tract of uremic patients could not be the reason for the decreased suppressive effect of the drug.

Previous studies have used probenecid as pharmacologic inhibitor of reabsorption of secreted urate in order to determine the relative role of this component in the urate homeostasis of normal subjects.[[4]], [[17]] Theoretically, the PB test has potential limitations in patients with renal failure. In normal subjects probenecid is by 99% bound to serum albumin and enters the urine largely by secretion.[[27]] A decrease of the bounded fraction of PB in uremic patients could result in a partial inhibition of presecretory reabsorption due to an increase of the filtered fraction of the drug. This could lead to an overestimation of postsecretory reabsorption in these patients. However, urate excretion values following either 2 or 4 g of PB remain stable.

Secretion of PB may well be altered as a result of the retention of several metabolites and PB absorption from the gastrointestinal tract may be ineffective. Therefore, an impaired accumulation of PB in tubular cells and/or fluid might appear in these patients. However, in previous studies by increasing the dose of PB no further uricosuria was observed.[[12]] It is also noteworthy that Lang et al.[[25]] attained maximum uricosuria in patients with chronic renal failure using 500 mg of PB only.

Uricosuric response to PB in patients with ADPKD and creatinine clearance 20–80 mL/min was markedly reduced when compared with CGNK patients and the same degree of renal failure.

Patients with ADPKD and chronic renal failure (creatinine clearance = 20–80 mL/min) showed a greater urate clearance and fractional urate excretion as well as lower plasma urate concentrations compared with glomerulonephritic patients (Table 1). Results from PZA and PB tests showed a normal PZA-suppressible urate, higher PZA-nonsuppressible urate and lower uricosuric response to PB in ADPKD patients (Table 2). According to Diamond's classification of various uricosuric states, a high urate clearance associated with normal PZA-suppressible, increased PZA-nonsuppressible urate excretion and normal or decreased uricosuric response is compatible with decreased reabsorption of filtered urate.[[15]] Uricosuric response or postsecretory reabsorption depends upon intact secretion, and secreted urate (indirectly estimated) is lower in ADPKD group (Table 1 and 2) (although tubular secretion cannot be accurately estimated). The estimation of the secreted urate as proposed by Garyfallos et al. and Magoula et al.[[12]], [[16]], [[21]], [[22]] and applied in the present study should be more accurate compared with other studies mainly in cases with inhibition of presecretory reabsorption.[[17]]

As renal failure becomes more severe, reabsorption of filtered urate decreases progressively and at a level of GFR less than 20 mL/min the urate that escapes presecretory reabsorption was 7.96% of the filtered amount in CGNK patients and 11.35% in the ADPKD respectively (Table 2). At this level of renal function ADPKD patients showed a urate clearance and excreted amount of urate per nephron higher than CGNK patients (Table 1 and 2). However, results in advanced renal disease should be interpreted with caution.

Among various factors that might account for these differences of tubular urate transport between ADPKD and CGNK patients urine flow rates and urine pH was similar in the two groups. Also, glucosuria was no detectable during clearance studies periods. However, a change of the extracellular fluid volume (EFV) or in renal blood flow may be possible causes of this difference. Especially for ADPKD patients with normal renal function no alterations in renal tubular sodium and water handling were detected.[[29]] However, has been reported, that under basal conditions, with deterioration of kidney function decreased proximal and distal reabsorption of sodium and water as well as increased atrial natriuretic factor (ANF).[[29]]

A curious paradoxical relationship between hypertension and ADPKD, namely lack of the depressing effect of hypertension on renal urate handling has been recently reported by Kaehny et al. with the suggestion that factors associated with hypertension in the ADPKD patients might at the same time enhance renal urate handling.[[10]] Atrial natriuretic factor (ANF) which can increase renal urate clearance appears increased in certain but not in all circumstances in hypertensive subjects with ADPKD patients.[[10]] On the other hand high ANF levels in normotensive glomerulonephritic patients have also been reported.[[28]]

In conclusion patients with ADPKD and normal renal function have normal renal urate handling and plasma urate levels within normal range. In contrast patients with CGNK and normal renal function showed statistically significant higher plasma urate levels than control subjects and this is attributed to a lower renal urate clearance and fractional urate excretion. With increasing severity of disease and during evolution of renal failure (Group B) CGNK patients showed higher urate plasma levels and lower renal clearances as well as fractional urate excretion comparing to ADPKD patients with the same degree of renal failure. The decreased reabsorption of filtered urate contributes to the increased per nephron urate excretion in chronic renal failure and is also responsible for the difference seen between two groups. Finally, when renal diseases become more advanced (Group C) there was no difference in renal urate handling between ADPKD and CGNK patients.