[The treatment of osteodystrophy in dialyzed uremic patients: results of the first Sardinian audit]. / Il trattamento dell'osteodistrofia nei pazienti uremici in dialisi: risultati del primo Audit sardo.

BACKGROUND: Hyperphosphatemia in the uremic patient undergoing dialysis causes and makes the secondary hyperpharatyroidism progress. Nowadays it has a very important role in predicting mortality. The aim of the study was to assess by "Audit" to analyse adequacy of the Sardinian dialytic patients with reference to the optimal objective of the national and international guidelines. PATIENTS AND METHODS: The questionnaire of the audit was composed of 11 questions about the percentage distribution of: calcium in the dialysate, values of phosphoremia), Ca x P product, patients treated with vitamin D taking one or more phosphate binders, average dose, spKt/V > or = 1.2, serum aluminium, parathiroidectomy. RESULTS: We examined 1274 dialysis patients (93% on hemodialysis and 7% in CAPD) in 26 dialytic centers in our region (age 63.8 anni +/- 32.4; dialytic age 5.15 +/- 5.06. Phosphorus ranges (mg/dL) P < 5.5: 61.3 +/- 23%; between 5.5 e 6.5: 28.2 +/- 17.7%; and P > 6.5: 10.4 +/- 7.7%; Ca x P (<60): 77.8% +/- 16.6%; between 60-70: 16.8 +/- 13.4%; > 70: 4.99 +/- 4.7%. The more prescribed dialysate calcium was 1.5 mmol/L in HD (58.8%) HF (60.6%), HDF (51.6%) and CAPD (5.6%). PTH levels were: 31.1% (<120); 29.5% (120-250); 21.1% (250-450); 8% (450-600); 10.3% (>600). Patients on vitamin D: os daily 23.04 +/- 28%; post-dialysis boluses: os 32.6 +/- 28, i.v. 10.6 +/- 9%; no therapy 32.7 +/- 22.7%. The percentage use of phosphorus binders: 48.5% calcium carbonate (2.9 g/d); 7.12% calcium acetate (1.34 g/d); 13.5% sevelamer (2.79 g/d); 10% total aluminium based (0.62 g/d). The aluminium is dosed in 11/26 dialysis units (32.3% of the population); 2.3% +/- 0.9% of patients having Aluminium > 30 mcg/L. The dialytic patients have a Kt/V > or = 1.2: 80.1 +/- 19%. Parathyroidectomy incidences 1.8%. CONCLUSIONS: The data show good control of the average phosporous, there is a worrying percentage of patients with PTH values compatible with hypodynamic bone condition, lower and therefore safer calcium levels in the dialysate, poor aluminium control and low incidence of parathyroidectomy. In our experience the audit is a good way to verify and to correct the therapeutic choice in uremic osteodistrophy.

Importance of liver interstitial pressure on sodium retention.

Experiments were performed on 23 dogs to assess the effect of splanchnic pooling on renal hemodynamics and Na retention. When the thoracic duct pressure was raised to 40 cm H2O (HTDP), liver interstitial pressure rose from 9.0 +/- 0.4 to 19.8 +/- 1.1 cm H2O. Simultaneously, glomerular filtration rate (GFR) and renal plasma flow fell in the left kidney from 16.3 +/- 1.7 to 9.6 +/- 1.3 and from 73.7 +/- 12.2 to 44.3 +/- 9.8 ml.min-1, respectively (p less than 0.01). UNa.V fell to 59 +/- 9% of control value (p less than 0.01). Plasma antidiuretic hormone (ADH) rose from 29.5 +/- 7.7 to 46.9 +/- 9.2 pg.ml-1 (p less than 0.05). When a portocaval shunt (PCS) was opened in 10 dogs during HTDP after the first set of experimental measurements, splanchnic pressure fell from 17.2 +/- 1.1 to 11.5 +/- 1.2 cm H2O, attended by a return towards control of GFR. ADH fell significantly to 16.5 +/- 8.1 during PCS, and to 9.7 +/- 1.5 pg.ml-1 during a last, postexperimental control period. Instead, UNa.V remained unchanged at the low levels measured during HTDP alone. When the HTDP was released in the 17 dogs without, and the 10 dogs with PCS, all variables became indistinguishable from control, except for UNa.V, which remained reduced, even in 4 aldosterone-escaped animals. No significant change in any of these variables occurred in 6 sham-operated control animals. These data demonstrate that it is possible to increase interstitial liver pressure through the lymph duct.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium reabsorption by the Henle loop in humans.

In a previous study, we described a new method [3] to measure Na reabsorption by each segment of the human nephron independently. Reabsorption was expressed as equivalent volumes of solute-free water (CH2O) generated by the loop of Henle (CH2O-HL) and by the distal tubule (CH2O-DT), and dissipated by back diffusion (BD) across collecting ducts (CH2O-BD). These data were obtained during maximal water diuresis (MWD). The present study was undertaken to calculate CH2O-HL by experiments performed during maximal antidiuresis (MA). For this purpose, a new theoretical approach was devised, described by algebraic equations which allowed calculations of segmental transport during MA alone, where only CH2O-HL could be calculated independently. The study was performed on 14 normal volunteers who were studied twice by clearance measurements, firstly during MWD and again during MA. In each experiment, clearance periods were performed during baseline conditions and during the administration of furosemide (0.7 mg/kg bolus injection followed by 0.06 mg/kg/min maintenance infusion). From the values measured during either condition, segmental reabsorption was calculated. During MWD, CH2O-HL averaged 19.4 + 10.4, during MA 20.4 + 8.0 ml/min/GFR X 100; p greater than 0.05. The paired measurements were significantly correlated (r = 0.80; p less than 0.01). These data demonstrate that CH2O-HL obtained with the original theory is a reproducible result that can be confirmed with independent measurements obtained during different experimental conditions. Thus, measurements of segmental Na transport in the human nephron are feasible and can contribute important informations on disease states.

Bartter's syndrome with normal chloride reabsorption during indomethacin treatment.

A 17-year-old male patient with Bartter's syndrome was admitted for renal function studies. This patient had persistent hypokalemia, first found at age 5; the diagnosis of Bartter's syndrome with renal hypersecretion of prostaglandins E2 and F2 alpha had been established at age 13. A congenital defect of chloride reabsorption was expected, but after 4 years of indomethacin treatment no such defect was found. Withdrawal of indomethacin for 1 week resulted in profound hypokalemia and the appearance of a chloride reabsorption defect, with an excessive urinary PGE2 and PGF2 alpha excretion, and a parallel decrease in plasma prostaglandin precursors. The cause of Bartter's syndrome in this patient seems to be renal hyperprostaglandinism.

[Diuretic and antihypertensive activity of azosemide]. / Attività diuretica ed antipertensiva dell'Azosemide.

The results of a study conducted using a new loop diuretic, Azosemide, on a group of 45 patients suffering from hypertension and oedema are reported. Thirty patients were studied in an open trial and in association with other drugs. The remaining 15 exclusively hypertensive patients, were studied in a controlled trial against Indapamide. The patient's standing and recumbent arterial pressure was monitored and all were given periodic weight checks. In the 1st group, Azosemide brought about a significant reduction in arterial pressure, without modifying body weight, but caused considerable weight loss (from 71 to 64 kg) (P less than 0,01) in the oedema patients without altering arterial pressure. In the 2nd group of hypertensive patients, a significant fall in arterial pressure (from 166 to 138 mmHg) was observed, most notably after Azosemide treatment. None of the patients revealed side effects, or alterations in laboratory parameters. It is therefore suggested that Azosemide--given its effectiveness and ease of application--is particularly useful for the diuretic treatment of hypertensive and oedematous patients.

Distal tubular sodium and water resorption in man.

It is possible to quantitatively estimate Na and water transport by each segment of the human nephron during maximal water diuresis (MWD) with a newly developed technique. The present study describes a new development whereby Na reabsorption by the ascending limb of Henle's Loop can be measured during a test of maximal antidiuresis (TMA) and compared with that obtained in separate experiments during MWD. In experiments performed on eight subjects, Henle's Loop reabsorption, expressed as equivalent volume of solute-free water generated, was 23.9 +/- 3.7 during MWD, 24.5 +/- 2.3 ml/min/100 ml GFR in TMA, p greater than 0.05; r = 0.68, p less than 0.05. Thus, our new method is reproducible and theoretically correct.

Demonstration of action of muzolimine on the serosal side of Henle's loop cells.

Muzolimine, a new diuretic, is known to act by inhibiting Na transport along the ascending limb of Henle's loop. Because of its ineffectiveness when perfused into the lumen, and as a result of experiments on frog skin, it is believed that muzolimine acts from the serosal cell side, unlike all other diuretics. We decided to assess the site of action of muzolimine (mucosa versus serosa) by experiments on rats. The animals were anesthetized, both ureters cannulated, and a hydronephrosis established in the left kidney by applying a counterpressure to the ureter, slowly and progressively increased up to 60 cm H2O in 3 minutes and kept stable for 20 minutes. Then either muzolimine 1.2 mg, or furosemide 4 mg, was injected i.v. together with 131I-Hypaque as a glomerular marker. Three minutes later the hydronephrosis was released in the left kidney by cutting the catheter, and urine collections were started simultaneously in both kidneys into 25 microliter glass capillaries, that were filled in continuous sequence and numbered progressively. In each urine sample from each glass capillary Na and 131I-Hypaque were measured. In 5 animals receiving furosemide, UNa rose in the left post-obstructed kidney and reached a plateau level by the 3rd to 5th sample. The rise in Na concentration, indicating delivery of urine whose Na reabsorption had been inhibited along the loop of Henle paralleled that in 131I-Hypaque, indicating that the diuretic and the glomerular marker had reached Henle's loop simultaneously, following filtration after the hydronephrosis had been discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of acute renal failure by diuretics.

Experiments were performed on 26 rats to evaluate the effect of furosemide and muzolimine in an experimental model of acute renal failure (ARF). After control clearance measurements from both the left and the right kidney, an acute hydronephrosis was produced on the left side only, to completely interrupt urine flow rate. At the 17th minute of stop-flow, placebo (4 animals), furosemide (4 mg i.v. in 5 animals) or muzolimine (1.2 mg i.v. in 5 rats) were injected and three minutes later the renal arteries were clamped bilaterally for 20 minutes. The arterial clamps and the left hydronephrosis were removed at the 20th minute of ischemia and then 5 consecutive clearance periods were performed from either side to assess recovery from post-ischemic ARF. There was no difference in the entity of GFR depression and speed of recovery of either kidney between placebo, muzolimine and furosemide. The left, post-hydronephrotic kidney consistently exhibited a post-ischemic renal function more depressed than that measured in the contralateral side, although the speed of recovery was the same. The ATP content of the renal tissue was significantly larger in the right kidney compared to the contralateral side in the group receiving furosemide. In the animals treated with muzolimine ATP was significantly depressed in both kidneys. In the post-ischemic period the urinary Na excretion and the fractional water excretion rose significantly with either diuretic compared to placebo. However, this did not influence the recovery in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of prostaglandins in Na retention of porta-cava shunted rats.

The importance of prostaglandins (PG) in Na and water retention of liver cirrhosis was studied in rats with porta-cava shunt (PCS) compared to control, non-shunted animals. Balance studies were performed in metabolic cages with diets of high, normal and low Na. An experimental phase, during which the animals received either 5 mg X kg-1 of indomethacin daily or placebo, was preceded by a control period and followed by a post-indomethacin period identical to the control phase. In each diet, indomethacin, but non placebo, caused a positive Na balance, correlated with Na intake, which in overall pooled data amounted to -1453 +/- 255 muEq in PCS rats, significantly larger than that measured in controls, of -295 +/- 320 muEq (P less than 0.01). This was attended by a reverse change in K balance of -35.6 +/- 349 muEq versus -1566 +/- 582 muEq (P less than 0.01); glomerular filtration rate (GRF) was unchanged. These data demonstrate that PGs contribute to the control of Na homeostasis in the presence of PCS.

Studies on the nephron segment with reduced sodium reabsorption during starvation natriuresis.

The segment of the nephron where carbohydrate deprivation depresses Na transport leading to natriuresis was sought by a new clearance technique designed to measure segmental reabsorption in each portion of the human renal tubule. Experiments were performed during maximal water diuresis before and 4 days after carbohydrate withdrawal. Proximal reabsorption had fallen from 70 +/- 4 to 60 +/- 5 ml X min-1, p less than 0.05, by the 4th day of sugar deprivation, accounting for the natriuresis and the associated weight loss of 1.8 kg. By the 4th day of fasting, when Na excretion had returned to control levels, GFR had fallen nonsignificantly from 99 +/- 6 to 95 +/- 5 ml X min-1, while Na reabsorption along distal segments had risen. In fact, Na transport, expressed by the equivalent volumes of solute free-water generated, rose from 17.4 +/- 3.4 to 23.6 +/- 2.1 along the ascending limb of Henle's loop, and from 8.1 +/- 0.8 to 9.2 +/- 1.3 ml X min-1 X GFR-1 X 100 along the distal tubule. Thus, analysis of segmental Na transport by this method discloses that starvation natriuresis is a proximal tubular event, progressively counterbalanced by enhanced Na reclamation in more distal sites. Volume contraction and the attendant fall in GFR concur to curb delivery out of the proximal tubule which is matched by enhanced distal Na reabsorption till a new steady-state excretion is attained.

Experimental dissociation of the effects of prostaglandins on renal sodium and water reabsorption by cyclo-oxygenase inhibitors in the rat.

1 The relative importance of the effect of prostaglandins on renal sodium and water reabsorption was assessed in rats. 2 Clearance experiments were performed on 24 anaesthetized rats divided into 3 groups. Each group was infused throughout either with Ringer solution at 9 ml/h (Protocol I), or at 3 ml/h (Protocol II) or with hypotonic fluid at 5 ml/h (Protocol III). Clearance periods were performed before and after intravenous injection of indomethacin (5 mg/kg) and then of aspirin (20 mg/kg). The natriuretic response to different degrees of volume expansion was not modified during the action of the inhibitors. 3 When baseline urine osmolality (Uosm) was high (Protocol II) no further increase occurred in the presence of prostaglandin inhibition. Conversely, Uosm rose from 771 +/- 134 to 1356 +/- 414 and from 575 +/- 245 to 841 +/- 407 mosm/kg (P less than 0.05) in Protocol I and Protocol III respectively, when antidiuretic hormone secretion was inhibited by the higher degree of volume expansion. 4 There was a significant correlation between the change in urine flow rate induced by cyclooxygenase inhibitors and the attendant variations in Na excretion, r = 0.42, n = 41, P less than 0.01. 5 Thus, prostaglandins affect Na loss during saline load as a side effect of their action on water permeability. They could play an important role in volume depletion by counterbalancing the large secretion rate of renal vasoconstrictors.