A. Borsatti

Increased Urinary Excretion of Renal Enzymes in Idiopathic Calcium Oxalate Nephrolithiasis

Urinary excretion of gamma-glutamyl transpeptidase, angiotensin I converting enzyme, beta-galactosidase and N-acetyl-beta-glucosaminidase was evaluated in 30 patients with idiopathic calcium oxalate urolithiasis. Higher than normal values were observed and the excretory enzyme pattern suggested tubular damage in patients with stones. A parallel study in the rat showed that an oxalate surcharge can promote increased urinary excretion of these enzymes. It is known that urothelium injury may enhance crystal adhesion. If the damage is primary it may be viewed as a promoting factor. If it is secondary it may be considered a factor capable of increasing salt precipitation.

RAISED TRANSMEMBRANE OXALATE FLUX IN RED BLOOD CELLS IN IDIOPATHIC CALCIUM OXALATE NEPHROLITHIASIS

Red-blood-cell transmembrane oxalate flux was measured in a group of patients with idiopathic calcium oxalate nephrolithiasis and in normal controls. The mean transmembrane oxalate flux rate was significantly higher in stone-forming patients than in controls (0.93 +/- SD 0.31/min vs 0.29 +/- 0.11/min). 80% of stone-forming patients showed raised (greater than 2SD above the mean in controls) transmembrane oxalate flux. Anomalous cellular oxalate transport may be an important pathogenetic factor in calcium oxalate nephrolithiasis.

Increased urinary NO2−/NO3− and cyclic guanosine monophosphate levels in patients with bartter's syndrome: Relationship to vascular reactivity

Nitric oxide (NO) is a potent endogenous vasodilator and plays a pivotal role in the control of vascular tone by the formation of cyclic guanosine monophosphate (GMP). Patients affected by Bartters syndrome have lower than normal vascular reactivity with normohypotension and decreased peripheral resistances in spite of biochemical and hormonal abnormalities typical of hypertension, and it is possible that increased production of NO may be involved in maintaining this reduced vascular response and vasodilatation. We have examined this possibility by studying NO2-/NO3- and cyclic GMP urinary excretions to assess NO production in vivo in seven patients affected by Bartters syndrome compared with seven healthy controls. A group of five patients with hypokalemia other than Bartter syndrome (pseudo-Bartters) was also included in the study to evaluate the effect of hypokalemia on NO production. NO2-/NO3- urinary excretion (0.45 +/- 0.14 v 0.25 +/- 0.04 micromol/micromol urinary creatinine [controls], P < 0.005, v 0.28 +/- 0.05 [pseudo-Bartters], P < 0.01) and cyclic GMP urinary excretion (0.057 +/- 0.028 v 0.022 +/- 0.01 micromol/micromol of urinary creatinine [controls], P < 0.009, v 0.024 +/- 0.004 [pseudo-Bartters], P < 0.02) were increased in patients with Bartters syndrome in comparison with controls and pseudo-Bartters, and a linear correlation between these two parameters was also present (P < 0.001). We conclude that in Bartters syndrome the increased NO2-/NO3- and cyclic GMP urinary excretions point to an increased NO synthesis, which could account for the reduced vascular response of the disease, therefore adding its role in determining the vascular hyporeactivity of Bartters syndrome.

Urinary glycosaminoglycans, sialic acid and lysosomal enzymes increase in nonalbuminuric diabetic patients.

Urinary excretion of glycosaminoglycans (GAGS) and sialic acid (SA), as well as the activity of two renal enzymes related to glycoprotein metabolism, N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (GAL), and two others unrelated to glycosaminoglycans and glycoprotein metabolism, gamma-glutamyltranspeptidase (gamma-Gt) and angiotensin-I-converting enzyme (ACE), were evaluated in 40 insulin-dependent diabetic patients with normal range albuminuria, 21 patients with mesangial glomerulonephritis, and 30 control subjects. Diabetic and glomerulonephritic patients excreted a significantly higher amount of GAGS and SA, and showed greater NAG and GAL activities; gamma-Gt and ACE levels were within normal ranges. No correlation could be demonstrated between diabetes duration and GAGS, SA, NAG and GAL findings. Moreover, no correspondence between degree of metabolic control, as reflected by glycosylated hemoglobin (HbA1a-c) and GAGS, SA, NAG and GAL emerged.

Prevalence of Hyperoxaluria in Idiopathic Calcium Oxalate Kidney Stone Disease

Urinary excretion of oxalate, calcium and urate has been investigated in 88 patients affected by idiopathic calcium oxalate stone disease and in 20 normal subjects. Of these ions, only oxalate was found significantly higher in stone formers. Defining hyperoxaluria as urinary oxalate excretion greater than 2 SD above normal, 50% of stone-forming people were found to be hyperoxaluric. When stone formers were classified in normo- and hyperoxaluric, the prevalence of hypercalciuria, hyperuricuria, family history of stone disease and recurrencies in stone formation was the same in both groups. It is concluded that hyperoxaluria is a frequent finding in finding in idiopathic calcium oxalate renal stone disease.

Carotid artery lesions in patients with nondiabetic chronic renal failure

Atherosclerotic complications are the leading cause of death in chronic renal failure (CRF) patients. Therefore, we wished to investigate the prevalence of carotid artery lesions (CALs) in these subjects. Two groups were evaluated by high-resolution echo Doppler: group 1 included 103 patients (68 males and 35 females) affected by nonnephrotic CRF and group 2 included 100 control subjects (60 males and 40 females). The prevalence of hypertension was 84% in both groups. The exclusion criteria included diabetes mellitus and symptoms of cerebrovascular disease. In the two groups we evaluated clinical history, physical examination, total cholesterol, triglycerides, fibrinogen, blood cell counts, blood urea nitrogen, creatinine, 24-hour proteinuria, and urine analysis. In group 1 patients the following lipid profile parameters were also evaluated: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), ApoAI, ApoAII, and ApoB. Group 1 had higher triglycerides and fibrinogen than group 2. A lower body mass index was found in group 1 than in group 2. The prevalence of CALs was significantly higher in the CRF patients than in the control subjects (62% v 47%; P = 0.04). The difference between the two groups was more striking among normotensive patients (62% v 19%; P = 0.03). All CRF patients affected by peripheral arterial disease and 86% of those having coronary artery disease had associated CALs. In CRF patients the severity of CALs was positively correlated to age, white blood cell count, triglycerides, and fibrinogen. Nondiabetic CRF patients have a higher prevalence of carotid artery lesions than control subjects. Several factors besides hypertension, including lipids, blood coagulation, and leukocytes, could contribute to the accelerated atherosclerosis of CRF patients.

Intracellular calcium signalling and vascular reactivity in Bartter's syndrome

We investigated patients affected by Bartters syndrome in the attempt to localize the intracellular defect mediating the reduced intracellular Ca2+ mobilization that may be responsible for the decreased vascular reactivity characteristic of Bartters syndrome. Using the formylmethionyl-leucyl-phenylalanine (fMLP) receptor system, which causes, intracellular calcium release, we investigated fMLP-stimulated intracellular inositol 1,4,5-trisphosphate (IP3) production as well as the number and affinity of fMLP receptors in neutrophils from Bartters syndrome patients and healthy controls. Scatchard plot analysis of radioactive fMLP binding to neutrophils indicated that there were no differences in either cell receptor number and affinity for ligand between healthy controls (n = 5) and patients with Bartters syndrome (n = 5): 6,151 +/- 1,431 vs. 7,112 +/- 2,566 receptors/cell; K(D): 0.446 +/- 0.14 vs. 0.454 +/- 0.09 pM of fMLP. 5- and 10-second fMLP-stimulated intracellular IP3 production was instead reduced in patients affected by Bartters syndrome: 2.479 +/- 1.07 vs. 4.073 +/- 1.04 nmol/10(7) cells at 5 s (n = 8; p < 0.01); 1.673 +/- 0.741 vs. 3.766 +/- 1.348 nmol/10(7) cells at 10 s (n = 8; p < 0.005). The results of this study indicate that the anomaly of intracellular calcium mobilization in patients with Bartters syndrome arises from a defect at the postreceptor level. The anomalous calcium signalling that takes place in Bartters syndrome may provide a mechanism for the hyporesponsiveness to pressor stimuli characteristic of these patients.

Kaliuresis in Normal Subjects following Oral Potassium Citrate Intake without Increased Plasma Potassium Concentration

Ingestion of potassium salts typically induces both a kaliuresis and an increase in the systemic plasma potassium concentration. In this study normal healthy adults undergoing water diuresis ingested potassium citrate or sodium citrate (0.5 mmol/kg body weight) or continued without ion ingestion (a time control group). Urine was collected over 20-min intervals and venous blood sampled at midinterval. Intake of potassium citrate led to a significant increase in potassium excretion that began during the first postingestion collection and peaked 60-80 min after intake with a maximal increase in potassium excretion above baseline of 1.60 mumol/min.kg-1. The kaliuresis occurred without changes in plasma potassium concentration, excretion of creatinine or calcium, or urine hypo-osmolality and was associated with a briefer, smaller, and less regular increase in sodium excretion and a pronounced but irregular increase in chloride excretion. Plasma aldosterone was insignificantly elevated above baseline, and the initial increase did not occur until 40-60 min after potassium intake. Intake of sodium citrate did not produce a kaliuresis. The cause of the kaliuresis does not appear to be an increased systemic plasma potassium concentration, an increased plasma level of aldosterone, intake of citrate, or an elevated excretion of sodium. The mechanism inducing the kaliuresis following oral potassium intake in the absence of changes in systemic plasma potassium may involve a reflex initiated at potassium sensors in gut, portal vein, or liver.

Nifedipine Can Preserve Renal Function in Patients Undergoing Aortic Surgery with Infrarenal Crossclamping

Sixteen patients diagnosed with an aneurysm of abdominal aorta or Leriche disease underwent elective aortic surgery involving crossclamping of infrarenal aorta (ICC). These patients were randomized into two equal groups and 8 patients were infused with nifedipine starting from the isolation of aorta until the end of surgery (group A) while another 8 patients were infused with low-dose dopamine (group B) over the same surgical course. Plasma endothelin (ET) was measured before the induction of anesthesia, at the beginning and at the end of the clamp period and at the end of the operation. Intraoperatively, creatinine clearance and urinary excretion of PGE2, 6-keto PGF1 alpha and TxB2 were also determined before, during and after aortic crossclamping. Preoperative GFR as well as preinduction cardiac index (CI) and pulmonary capillary wedge pressure (PCWP) of the two groups did not differ. During cross-clamping plasma ET rose significantly in both groups. However, after clamp removal, plasma ET decreased in group A while it remained elevated in group B. Urinary excretion of TxB2, PGE2 and 6-keto PGF1 alpha increased during clamp in both groups, but the ratio of PGE2 + 6-keto PGF1 alpha/TxB2 during and after clamp was significantly higher in group A than in B. Postclamp creatinine clearance decreased in group B, and increased in group A; postoperative value of GFR was unchanged in group A and decreased significantly in group B. In conclusion, infusion of nifedipine, in contrast to dopamine, prevented the decrease of GFR in patients undergoing aortic surgery. This effect could be mediated by a nifedipine modulation of ET vascular synthesis and/or a preferential renal synthesis of vasodilating prostanoids.

Juvenile Renal Stone Disease: A Study of Urinary Promoting and Inhibiting Factors

Urinary excretion of the most widely studied renal stone promoting (calcium, oxalate, uric acid and phosphate) and inhibiting (citrate, magnesium, pyrophosphate and glycosaminoglycans) factors, as well as the Tamm-Horsfall mucoprotein, was evaluated in 14 children with idiopathic calcium nephrolithiasis, 6 children with renal stone disease secondary to excretory malformations and 19 normal controls. No statistically significant differences in urinary excretion of promoting and inhibiting factors were found in children with idiopathic calcium nephrolithiasis but the relationship between promoting and inhibiting factors was changed as shown by an abnormal ratio of oxalate/citrate X glycosaminoglycans. This finding suggests that there is an imbalance between promoting and inhibiting factors in children with idiopathic calcium nephrolithiasis, and it is not detected by assay of each single substance.