Insulin-dependent diabetes and renal hypouricemia

We studied 14 patients (11 women and 3 men) from 18 to 33 years old, suffering from type I diabetes mellitus with normal renal function (creatinine clearance 106.91 +/- 28.73 ml/min) and serum uric acid below 2.5 mg/dl (2.34 +/- 0.11 mg/dl) as well as a high uric acid clearance (23.04 +/- 5.92 ml/min) and fractional urate excretion (21.4 +/- 2.6) versus urate clearance 9.82 ml/min and fractional urate excretion 8.80 +/- 1.3 in 14 normal control subjects. The study of the uricosuric mechanisms was conducted by the combination of probenecid (PB) test which inhibits the reabsorption of secreted urate, and pyrazinamide (PZA) test, which inhibits its tubular secretion. The results of studies indicate that the increase in urate clearance was accounted for by increased PZA-nonsuppressible urate suggesting a decreased reabsorption of filtered urate. Increased PZA-suppressible urate excretion combined with impaired response to a uricosuric drug is consistent with impaired reabsorption of secreted urate. According to our findings, increased urate excretion in diabetic patients may be attributed to the inhibition of both filtered and secreted reabsorption. This reabsorptive tubular abnormality is consistent with the view of an interference of tubular reabsorption of glucose with the tubular capacity for uric acid reabsorption.     

Effect of valsartan on renal handling of uric acid in healthy subjects

OBJECTIVE: To evaluate the effect of valsartan on renal handling of uric acid in healthy subjects. METHODS: A randomized, single-blind, placebo-controlled clinical trial was performed in twelve healthy volunteers. Six received a morning dose of valsartan 80 mg orally during 14 to 21 days and the other six received placebo. Before and after valsartan or placebo, clearance, fractional excretion and excretion uric acid rates were calculated. Presecretory reabsorption, tubular secretion and postsecretory reabsorption of uric acid were assessed by pharmacological tests using pyrazinamide or probenecid. RESULTS: There were no differences in clearance, fractional excretion and excretion uric acid rates with valsartan and placebo. Valsartan did not affect presecretory reabsorption (p = 0.92), tubular secretion (p = 0.62) or postsecretory reabsorption (p = 0.52) of uric acid. CONCLUSION: Valsartan did not significantly affect renal handling of uric acid in healthy subjects.     

Lack of effect of salt intake on urinary uric acid excretion

Although it has been established that acute expansion of the extracellular fluid volume results in enhanced uric acid clearance, the effect of chronic volume expansion by a high salt diet on urinary uric acid excretion has not been examined. Eleven normal subjects were placed on a constant diet containing 10 mEq. sodium per day for 10 days, followed by 240 mEq. sodium daily for another 10 days. Measurements were performed on the final 3 days of each phase. Urinary sodium increased from 9 plus or minus 3 standard error to 221 plus or minus 9 mEq. per day (p less than 0.001), and uric acid clearance increased from 5.9 plus or minus 0.4 to 7.1 plus or minus 0.6 ml. per minute (p less than 0.01). However, serum uric acid decreased from 6.4 plus or minus 0.4 to 5.5 plus or minus 0.3 mg./dl. (p less than 0.001). Total urinary excretion of uric acid did not change (533 plus or minus 24 to 535 plus or minus 26 mg. per day). A high salt diet does not result in sustained hyperuricosuria, although it may predispose to kidney stone formation in other ways.     

The effect of trimethoprim on potassium and uric acid metabolism in normal human subjects

BACKGROUND: Trimethoprim used in combination with other antibiotics, has been implicated in causing hyperkalemia and hypouricemia in patients with acquired immune deficiency syndrome (AIDS). In experimental animal models, trimethoprim has been demonstrated to block sodium channels and Na+-K+-ATPase in the distal nephron and thus impair potassium excretion. Although the data from the experimental models suggest that trimethoprim reduces urinary potassium excretion, the retrospective clinical studies have confounding factors that prevent a rigorous demonstration that the hyperkalemia and hypouricemia are due solely to the effects of trimethoprim on solute excretion. AIM: The purpose of this study was to evaluate the effect of trimethoprim on potassium and uric acid balance in normal human subjects. METHODS: Five normal human subjects were admitted to the general clinical research center and placed on a fixed metabolic diet. After a 4-day control period, the subjects were given trimethoprim (15 mg/kg/day) orally for 5-7 days followed by a 4-day recovery period. Free-flow blood samples and 24-hour urine collections were obtained daily. RESULTS: Treatment with trimethoprim resulted in a significant increase in plasma potassium concentration (4.5 +/- 0.1 versus 3.7 +/- 0.1 mmol/l, p < 0.005) and significant decrease in serum uric acid concentration (3.8 +/- 0.4 versus 5.6 +/- 0.5 mg/dl, p < 0.001). Treatment with trimethoprim significantly increased the urinary excretion of uric acid, but did not significantly decrease potassium excretion during the 7-day treatment period. There was, however, a significant decrease in potassium excretion observed during the first 48 hours of trimethoprim treatment. In one subject where repeat studies were performed using different dosages, the effect on potassium and uric acid levels appeared to be dose-dependent. CONCLUSIONS: Trimethoprim increases plasma potassium concentration probably by reducing urinary potassium excretion. Trimethoprim decreases serum uric acid levels by augmenting urinary uric acid excretion. This uricosuric effect may be due to the ability of trimethoprim to impair urate reabsorption by the urate-anion exchanger in the proximal tubule.     

An evaluation of the physicochemical risk for renal stone disease during pregnancy

Seventeen subjects were studied during the third trimester of pregnancy (PG) and post partum (NPG) to evaluate the effect of pregnancy on the physicochemical risk of renal stone disease. Levels of urinary saturation for calcium oxalate (CaOx), brushite (Br), uric acid (UA), and monosodium urate (NaU) were determined as well as urinary excretions of stone-forming elements. In addition to urinary calcium excretion, assessment of calcium metabolism included serum calcium and parathyroid hormone. Urinary calcium excretion was 251 +/- 127 mg/day during pregnancy and 121 +/- 67 mg/day post partum (p < 0.001). This was associated with a higher intake of dietary calcium and altered renal handling of calcium with an increase in the filtered load and a decrease in renal tubular reabsorption. The increase in urinary calcium resulted in a higher level of saturation of the urine for calcium oxalate (NPG 2.1 +/- 1.0 vs PG 3.0 +/- 1.1, p < 0.02) and brushite (NPG 1.2 +/- 0.9 vs PG 1.9 +/- 1.1, p < 0.05) compatible with an increased risk of stone formation.     

Evaluation of renal handling of uric acid in essential hypertension: hyperuricemia related to decreased urate secretion.

The tubular transport of urate was studied in 40 hypertensive patients and in 20 normal subjects by means of pyrazinamide and benzbromarone tests. There was a marked decrease in urate excretion per nephron in hyperuricemic patients with essential hypertension. Serum uric acid correlated inversely with fractional excretion of urate (r = -0.7450, p less than 0.001). Presecretory and postsecretory reabsorption of urate did not significantly differ between hypertensive patients with high uric acid levels and control subjects. Urate secretion was significantly reduced in hypertensive patients and in those with hyperuricemia showed a twofold decrease. Serum uric acid correlated inversely with tubular secretion of urate (r = -0.7091, p less than 0.001) in hypertensive patients. These findings indicate that impaired tubular secretion of urate is a potential mechanism of hyperuricemia in essential hypertension.     

Urine calcium excretion, nephrogenous cyclic-adenosine monophosphate and serum parathyroid hormone levels in patients with essential hypertension.

To evaluate the role of calcium and the parathyroid gland in the pathophysiology of essential hypertension, creatinine clearance, urinary excretion of sodium, calcium and nephrogenous cyclic adenosine monophosphate (NcAMP) and serum parathyroid hormone (PTH) levels were measured in 25 newly diagnosed essentially hypertensive patients before institution of any treatment and in 25 age- and sex-matched normal volunteers. While no significant differences in creatinine clearance, serum total calcium levels or 24-hour sodium excretion existed between the two groups, hypertensives had a higher mean (+/- SD) 24-hour calcium excretion rate (199.0 +/- 44.7 vs. 152.8 +/- 33.6 mg, p less than 0.001), a higher mean NcAMP excretion rate (2.54 +/- 0.8 vs. 1.87 +/- 0.5 nmol/100 ml glomerular filtrate, p less than 0.001) and a higher mean serum PTH concentration (1.87 +/- 0.6 vs. 1.53 +/- 0.4 ng/ml, p less than 0.001) than the normotensives. A significant positive correlation existed between calcium and sodium excretion in both hypertensives (r = 0.66, p less than 0.001)) and normotensives (r = 0.67, p less than 0.001), but given the same levels of creatinine clearance and sodium excretion, hypertensives excreted more calcium than normotensives (p less than 0.001)). In both hypertensives and normotensives, serum PTH levels were positively correlated with NcAMP excretion (r = 0.42, p less than 0.05, and r = 0.41, p less than 0.05, respectively) and the ratio of urinary sodium to urinary calcium excretion (r = 0.59, p less than 0.001, and r = 0.75, p less than 0.001), respectively). The above results suggest that in essential hypertension, increased activity of parathyroid glands may occur as a consequence of increased urinary calcium losses which are presumably due to an intrinsic defect in renal calcium handling.     

Relationship between aldosterone and sodium, potassium, and uric acid clearance in cirrhosis with and without ascites

We have suggested that cirrhotic patients with high uric acid clearances had an increased effective vascular volume. This hypothesis was tested by studying the relationship between the excretion of uric acid, sodium, potassium, and aldosterone in cirrhosis. In 29 consecutive cirrhotic patients, of whom 17 had ascites, and in a control group, the logarithm of urinary sodium and aldosterone excretion highly correlated in control (r = -0.79, p less than 0.001) and cirrhotic patients without (r = -0.72, p less than 0.01) and with (r = -0.80, p less than 0.001) ascites. The regression line significantly shifted to the left in the cirrhotic patients (p less than 0.001). The urinary ratio K/K + Na also correlated with urinary aldosterone in controls (r = +0.66, p less than 0.001) and in cirrhotic patients (r = +0.77, p less than 0.001); this regression line shifted to the right in cirrhosis patients (p less than 0.02). The fractional uric acid excretion significantly correlated with urinary aldosterone only in cirrhotic patients (r = -0.76, p less than 0.001). These data confirmed the existence of hypoaldosteronism in many cirrhotic patients and are consistent with tubular hypersensitivity to aldosterone and emphasize the major role of the effective vascular volume in the control of urid acid clearance in cirrhosis.     

Silicon metabolism. I. Some aspects of renal silicon handling in normal man

Renal silicon handling was investigated in 23 healthy adults using electrothermal atomic absorption techniques. The mean urinary silicon excretion was 33.1 +/- 3.85 mg/day; the mean renal silicon clearance was 88.6 +/- 7.94 ml/min; the mean fractional excretion of silicon was 86.35 +/- 8.1%, and the mean urine silicon concentration was 0.265 micrograms/ml. Using multiple correlation analysis, the urinary silicon was found to be highly significantly correlated with the urine magnesium concentration (p less than 0.001) and also with urinary sodium and urinary osmolality (p less than 0.01). 24-hour urinary silicon excretion was highly significantly correlated with fractional excretion of silicon (p less than 0.001), sodium (p less than 0.001), phosphorus (p less than 0.001), magnesium (p less than 0.001), and osmolar load. In split urine studies in 7 subjects urinary silicon was correlated highly significantly with urinary magnesium in all 7 and with urinary osmolality, urine calcium, and urine creatine concentration in 6 of 7. There was a highly significant correlation between renal silicon clearance and fractional excretion of silicon (p less than 0.0005), with magnesium excretion (p less than 0.01), and with sodium excretion. It is suggested that ion pairing of orthosilicate and magnesium may explain some of these urinary findings.     

Physicochemical metabolic characteristics for calcium oxalate stone formation in patients with gouty diathesis

PURPOSE: We determined why calcium oxalate stones instead of uric acid stones form in some patients with gouty diathesis. MATERIALS AND METHODS: Gouty diathesis was diagnosed from absence of secondary causes of uric acid stones or low urinary pH, and reduced fractional excretion of urate with discriminant score of the relationship between urinary pH and fractional excretion of urate less than 80. From the stone registry 163 patients with gouty diathesis were identified, including 62 with uric acid stones (GD + UA) and 101 patients with calcium oxalate stones (GD + Ca). Metabolic data and 24-hour urinary chemistry study were compared between the 2 groups. RESULTS: Compared with GD + UA, GD + Ca had significantly greater urinary calcium (196 +/- 96 mg per day vs 162 +/- 82 mg per day, p <0.05) and significantly lower urinary citrate (430 +/- 228 vs 519 +/- 288 mg per day, p <0.05), resulting in higher urinary saturation of calcium oxalate. Both groups had low urinary pH (less than 5.5) and high urinary undissociated uric acid (greater than 100 mg/dl). Urinary calcium post-oral calcium load was significantly higher in GD + Ca than in GD + UA (0.227 vs 0.168 mg/dl glomerular filtrate, p <0.001). CONCLUSIONS: Calcium oxalate stones may form in some patients with gouty diathesis due to increased urinary excretion of calcium and reduced excretion of citrate. Relative hypercalciuria in GD + Ca may be due to intestinal hyperabsorption of calcium.     

Urinary excretion rate of guanidinoacetic acid as a new marker in hypertensive renal damage

This study was undertaken to evaluate the relation between the urinary excretion of guanidinoacetic acid (GAA) and other substances in hypertensive patients (6 with borderline hypertension and 29 with hypertension) and 12 normal controls. In 10 of the hypertensive patients, GAA was measured before and after 4 weeks of treatment with calcium entry blocker. In hypertensive patients the rate of GAA urinary excretion was 43.5 +/- 17-4 micrograms/min, which was much lower than in the controls (77.2 +/- 35.9 micrograms/min) (p less than 0.01). There was no significant difference among these groups in creatinine clearance (CCr), serum creatinine (Cr), beta 2-microglobulin (BMG) or in the urinary excretion of BMG, N-acetyl-D-glucosaminidase (NAG) or radiosensitive microalbumin (mAlb). The urinary excretion rate of GAA was positively correlated with CCr (r = 0.62; p less than 0.01), and negatively correlated with mean blood pressure (r = -0.49; p less than 0.01). Finally, the GAA excretion was significantly correlated with urinary NAG (r = 0.24; p less than 0.05) and serum BMG (r = -0.31; p less than 0.05), but not with urinary mAlb (r = 0.12; p less than 0.05). Ten hypertensive patients followed for 4 weeks attained their ultimate mean blood pressure reduction after treatment (from 119.3 +/- 8.0 to 101.7 +/- 13.5 mm Hg; p less than 0.001), but the GAA/Cr ratio in the urinary excretion was significantly elevated (from 0.054 +/- 0.016 to 0.070 +/- 0.02; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of albumin infusion on the urinary excretion of beta2-microglobulin in patients with proteinuria

Most filtered proteins are reabsorbed by the renal proximal tubule by a mechanism that involves binding to the brush border membrane and endocytosis. Under normal conditions the low-molecular-weight protein beta2-microglobulin (beta2M), which is used to detect tubular injury, is reabsorbed almost completely. However, in proteinuric patients an increased urinary excretion of beta2M may not simply reflect tubular damage but might also result from a decreased tubular reabsorption due to competitive mechanisms. To examine the magnitude of such an effect we have studied the renal effects of albumin infusion (40 g in 2 h of a 20% solution) in 10 patients with a glomerular disease and proteinuria >3.5 g/24 h. Before, during and after albumin infusion the GFR (inulin clearance), RPF (PAH clearance), blood pressure and the urinary excretion of albumin, IgG, transferrin and beta2M were measured. Albumin infusion resulted in a slight decrease of the GFR (72 +/- 11 ml/min before and 67 +/- 10 ml/min after infusion), an increase of the RPF (379 +/- 66 ml/min before and 445 +/- 83 ml/min after), a decrease of the filtration fraction (0.20 before and 0.17 after), and hemodilution. After infusion the urinary excretion of albumin increased from 4.5 +/- 0.7 to 8.4 +/- 1.6 mg/min (p < 0.05). The urinary excretion of IgG and transferrin increased, probably reflecting a change in glomerular size-selectivity. In contrast, the urinary excretion of beta2M did not change significantly (baseline 12 +/- 5 microg/min, end 13 +/- 6 microg/min, percentage change 16.8 +/- 11%). To correct for changes in tubular load we calculated the fractional reabsorption of beta2M. The initial rise in albuminuria during infusion did not affect fractional tubular reabsorption (Delta%: 0. 72 +/- 0.52%, median 0.005%). In the period after infusion a slight decrease was noted (median -0.33%, p < 0.01). A decrease in the fractional reabsorption was particularly observed in patients with pre-existing tubular damage. In conclusion: infusion of albumin in proteinuric patients has no clinically relevant effect on the tubular reabsorption of beta2M. Therefore, beta2M is useful as a parameter to detect tubular injury and alterations in tubular handling of proteins in patients with proteinuria and glomerular diseases.     

Urinary calcium excretion in toxemia of pregnancy

The amount of urinary calcium excretion is an useful marker for distinction between patient with preeclampsia and normal pregnancy of chronic hypertension has been reported. This study was performed to investigate the extent and the etiology of decrease in urinary calcium excretion in toxemia of pregnancy. The subjects in this study were 20 patients with severe toxemia of pregnancy (group T) and 20 subjects with normal pregnancy (group N). In these subjects, serum calcium (s-Ca), phosphate (s-Pi) and uric acid (s-UA) and urinary calcium (u-Ca), phosphate (u-Pi) and uric acid (u-UA) were measured. The values of u-Ca and u-Pi in the group T were significantly decreased than the group N (p less than 0.001, p less than 0.01). The values of s-Ca and s-Pi made no distinction between group T and group N. There was significant relationships between u-Ca and, s-UA (r = -0.70), clearance of UA (r-0.82), Ccr (r = 0.64), and FEca: Cca/Ccr (r = 0.87). These results indicated that the decrease of u-Ca was evident in severe toxemia of pregnancy. And the decrease of u-Ca has resulted from increase of tubular reabsorption. The change of u-Ca of patients with toxemia was studied. After the onset of toxemia, u-Ca was decreased rapidly (less than 50 mg/day) and u-Ca was restored to the normal range (more than 100 mg/day) promptly after delivery. The value of u-Ca was over 100 mg/day in the second pregnancy that developed on toxemia of pregnancy among the cases who has severe toxemia in the first pregnancy. However, toxemia of pregnancy have relapsed in the case with low u-Ca excretion of less than 100 mg/day during the second pregnancy.     

Urinary excretion of endothelin-1 in normal subjects and patients with renal disease

To elucidate the pathophysiological significance of urinary endothelin-1 (ET-1), we measured urinary excretion of ET-1-like immunoreactivity (L1) in 17 patients with renal disease and 9 normal subjects. Twenty-four hour urinary ET-1-L1 excretion in patients with renal disease (358 +/- 68 ng, mean +/- SE) was significantly (P less than 0.005) greater than that of normal subjects (77 +/- 5 ng). In patients with renal disease. ET-1-L1 clearance (CET) exceeded creatinine clearance (CCR); CET/CCR (305 +/- 81%) was significantly (P less than 0.005) greater than that of normal subjects (43 +/- 13%). The 24-hour urinary excretion of ET-1-L1 in patients with renal disease showed significant correlation with that of N-acetyl-beta-D-glucosaminidase (r = 0.587, P less than 0.05), beta 2-microglobulin (r = 0.614, P less than 0.01) and albumin (r = 0.484, P less than 0.05). Intravenous infusion of saline (500 ml) in seven normal subjects did not affect urinary ET-1 excretion rate. These data suggest that urinary excretion of ET-1 derives mainly from renal tubular secretion at least in patients with renal disease, and that degradation and/or reabsorption of ET-1 at the tubular site may also contribute to the renal handling of ET-1. Therefore, urinary excretion of ET-1 should serve as a potential marker for renal injury.     

Silicon metabolism. II. Renal handling in chronic renal failure patients

In 36 patients suffering from chronic renal failure (mean creatinine clearance 26 ml/min), serum silicon levels were significantly increased (mean 0.52 microgram/ml compared with 0.265 microgram/ml in normals; p less than 0.005). Urinary silicon excretion per 24 h was significantly decreased (15.71 mg/24 h compared with 21.4 mg/24 h in normals; p less than 0.001). Fractional excretion of silicon (FESi) was significantly increased in chronic renal failure (p less than 0.001), with overall tubular secretion of silicon in 33% of patients. Urinary excretion of silicon was significantly related to urinary calcium excretion (p less than 0.0001) urinary magnesium excretion (p less than 0.0001) creatinine clearance (p less than 0.05) and sodium excretion (p less than 0.05). It is suggested that urinary silicon is in the form of orthosilicate, principally bound to calcium and magnesium; and that in chronic renal failure the increase in FESi, and the decrease in absorbed Si from the gastrointestinal tract, moderate the increase in plasma silicon levels and prevent excessive entry of silicon into the tissues.     

Renal hemodynamic and tubular response to furosemide in man during normal and restricted sodium intake

To investigate the factors determining the natriuretic response to furosemide (F) during Na restriction, we performed clearance studies in 7 healthy humans on a daily Na intake of 200 and 20 mmol. The maximum urine flow during water loading (Vmax) and simultaneous F administration was used as index of tubular fluid output from the proximal tubules. The F-induced natriuresis was only moderately reduced during Na restriction (Na excretion on low vs. normal Na intake: 4.28 +/- 0.25 vs. 4.94 +/- 0.25 mmol/min; p less than 0.05). The diminished natriuresis was mainly due to a significant fall in Na delivery to Henle's loop of 0.51 +/- 0.10 mmol/min which was either caused by a decrease in filtered Na load or a rise in fractional proximal reabsorption. Fractional distal Na reabsorption was less suppressible by F during Na restriction, but this contributed relatively little (0.15 +/- 0.11 mmol/min) to the total reduction in Na excretion (0.66 +/- 0.10 mmol/min). The F-induced increases in uric acid, phosphate, and bicarbonate excretion suggest an additional proximal site of action of F. This was confirmed by a rise in lithium clearance (CLi), another alleged index of tubular fluid delivery from the proximal tubules. However, the magnitude of the rise in CLi to values markedly exceeding Vmax suggest that CLi overestimates tubular fluid delivery to Henle's loop during F administration.     

The effect of acute and chronic protein loading on urinary pepsinogen A excretion

In 8 healthy male volunteers, urinary excretion (UE) and fractional clearance (FC) of pepsinogen A (PGA), beta 2-microglobulin (beta 2-m) and albumin were measured after 6 days high protein diet (HPD; 2.0 g/kg/day) and compared to values obtained after 6 days low protein diet (LPD; 0.5 g/kg/day). In addition, the effect of an acute protein load (APL; 500 g beef) on these variables were measured. Both chronic and acute protein loading induced a rise in glomerular filtration rate (GFR) of about 10% together with a parallel rise in effective renal plasma flow. UE PGA and FC PGA increased both after HPD (UE PGA 1,707 +/- 1,106 ng/min; FC PGA 23 +/- 12%) as compared to LPD (UE PGA 1,200 +/- 987 ng/min, p less than 0.01; FC PGA 18 +/- 12%, p less than 0.05), and after APL (UE PGA 2,276 +/- 1,389 ng/min; FC PGA 26 +/- 16%) as compared to baseline (UE PGA 1,418 +/- 965 ng/min, p less than 0.02; FC PGA 21 +/- 12%, p less than 0.05). UE and FC of beta 2-m and albumin were not affected by protein loading. As PGA is nearly freely filtered, it is concluded that the increase in fractional PGA clearance reflects a decrease in fractional tubular PGA reabsorption. Our results suggest that an increase in fractional protein clearance after protein loading is not necessarily due to an impaired glomerular permselectivity but represents a decreased fractional tubular reabsorption as a result of a GFR-mediated increase in filtered load without a concomitant increase in tubular reabsorption.     

Renal function before and after unilateral nephrectomy in renal donors.

Measurements of glomerular filtration rate (GFR), effective renal plasma flow (ERPF), tubular maximum reabsorption of glucose (Tmglucose) and secretion of para-aminohippurate (Tmpah), clearance of inorganic phosphate (Cphosphate) and uric acid (Curic acid), urine diluting capacity (CH2O) and urinary net acid excretion (UH + V) were made before and 10 to 14 days after unilateral nephrectomy in seven healthy renal donors. Comparisons were made between the functions of the remaining kidney and 50% of pre-uninephrectomy values. Mean post-uninephrectomy GFR increased by 36%, and mean ERPF, 55%. Tmglucose, Tmpah, Cphosphate, uric acid, CH2O, UH + V increased significantly, after uninephrectomy. The increase in Tmpah, Tmglucose and CH2O is proportional to the rise in GFR while the increase in Cphosphate, Curic acid and UH + V is proportionally greater than the increase in GFR. The changes in post-uninephrectomy renal handling of phosphate are not due to an increase in parathyroid hormone secretion.     

Biochemical profile of idiopathic uric acid nephrolithiasis

BACKGROUND: The objective of this study was to elucidate a biochemical profile of patients with idiopathic uric acid nephrolithiasis, without secondary causes (such as dehydration or diarrhea). Study subjects comprised 56 patients with idiopathic uric acid nephrolithiasis (UA stone group) who underwent a full outpatient evaluation. The control group was composed of 54 with absorptive hypercalciuria and 2 normal subjects, matched with the UA stone group according to age, body mass index, and gender. METHODS: Urinary pH and ammonium and serum and urinary uric acid were measured. The fractional excretion of urate was calculated. RESULTS: Compared with the control group, the UA stone group had a significantly higher serum uric acid and significantly lower urinary uric acid, pH (5.34 +/- 0.23 vs. 6.17 +/- 0.36, P < 0.001), and fractional excretion of urate (0.052 +/- 0.028 vs. 0.080 +/- 0.029, P < 0.001), but individual values overlapped considerably between the two groups. Discriminant analysis of the relationship between urinary pH and fractional excretion of urate yielded a "discriminant score," which provided a much better separation between the two groups, with a correct classification in 95.5% of subjects. In contrast, urinary ammonium, citrate, sulfate, and potassium did not differ between two groups. CONCLUSIONS: In idiopathic uric acid nephrolithiasis, urinary pH and fractional excretion of urate are significantly lower than in control subjects, suggestive of defects in urinary acidification and urate excretion. Since these impairments are believed to be associated with primary gout, the underlying disturbance in idiopathic uric acid nephrolithiasis may be primary gout.     

Effects of perfusion pressure and renal flow upon albumin excretion in isolated perfused kidneys

To explore the effects of renal hemodynamics upon urinary albumin excretion, sequential changes in perfusion pressure and/or flow were performed in isolated perfused rat kidneys. Elevation of perfusion pressure from 90 to 130 mm Hg increased renal flow from 48.9 +/- 1.1 to 54.3 +/- 1.4 ml/min and glomerular filtration rate (GFR) from 0.37 +/- 0.03 to 0.81 +/- 0.06 ml/min (p less than 0.001). Despite more than a doubling in GFR, albumin excretion remained unchanged (from 252 +/- 53 to 167 +/- 36 micrograms/min, p not significant), resulting in a decreased fractional clearance of albumin (theta) from 0.009 +/- 0.002 to 0.004 +/- 0.005 ml/min (p less than 0.01). To dissociate the effects of flow from those of pressure, angiotensin II was infused to decrease renal flow from 49.9 +/- 0.6 to 38.7 +/- 0.6 ml/min (p less than 0.001), while keeping perfusion pressure constant at 96 +/- 1 mm Hg. Although GFR was essentially unchanged (from 0.59 +/- 0.02 to 0.65 +/- 0.05 ml/min, p not significant), albumin excretion increased from 68 +/- 8 to 151 +/- 21 micrograms/min (p less than 0.001) and theta rose from 0.002 +/- 0.000 to 0.005 +/- 0.001 (p less than 0.02). Whole kidney hemodynamics acutely affect renal excretion of albumin in isolated kidneys.