We investigated, whether plasma cyclic guanosine 3':5'-monophosphate (cGMP) may be suited as a marker of hyperhydration in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In 81 HD patients the levels of atrial natriuretic peptide (ANP) and cGMP were markedly elevated before HD (ANP: 165 +/- 11.1 pg/ml; cGMP 43.5 +/- 2.2 pmol/ml). Significantly lower values (P < 0.01) were found after HD (ANP: 97 +/- 8.4 pmol/ml; cGMP 19.5 +/- 1.5 pmol/ml). Twenty-three patients had cGMP levels above 20 pmol/ml after HD. Therefore "dry body weight" was reduced in these patients. This resulted in a "normalization" of cGMP values to a postdialytic range below 20 pmol/ml in the majority of patients. All seven patients with persistently high cGMP levels despite weight reduction had left sided heart failure. In 33 CAPD patients ANP was slightly lower than after HD (68 +/- 10.4 pg/ml), and the cGMP level (22.4 +/- 2.3 pmol/ml) was between pre- and postdialytic values in HD. In eight CAPD patients with clinical signs of hypervolemia plasma cGMP, but not ANP, was significantly elevated. We conclude that the plasma cGMP level appears to be a reliable marker for fluid overload in patients on renal replacement therapy with normal heart function.

Determining a dialysis patient`s dry-weight is an exercise that oftentaxes the clinical judgement of even the most astute nephrologist. This is all the more true for CAPD, where undetected hyperhydration may be even more frequent than in hemodialysis, because patients treat themselves at home and the ultrafiltration volume is less well predictable. Therefore, a reliable and easily accessible biochemical marker for the detection of fluid overload would substantially enrichthe diagnostic manual. It has repeatedly been shown that in chronic hemodialysis patients, the plasma levels of the atrial natriuretic peptide (ANP) and of its second messenger cyclic GMP (cGMP) are markedly elevated. The levels of both substances fall during ultra- filtration and thus reflect the hydration state. Previous studies from our laboratory have demonstrated a particularly close relation between the postdialytic plasma cGMP level and the hydration state in chronic hemodialysis patients. There are only few data on ANP and cGMP levels in CAPD. We conducted the following study in order to determine ANP and cGMP levels in patients treated with CAPD, to compare them with the ones found in hemodialysis and to assess their value as markers of fluid overload.

The postdialytic plasma level of cGMP, a marker for the release of atrial natriuretic peptide (ANP) in humans, is closely related to hypervolemia in chronic hemodialysis patients. In order to test the practicability of routine postdialysis cGMP determination for the detection of fluid overload, ANP and cGMP levels in the total hemodialysis population of 81 patients were measured with blood samples drawn immediately after hemodialysis. Twenty-three patients had a cGMP level of more than 20 pmol/mL. In 13 of these, pulmonary congestion was present on the chest roentgenogram. Two of these patients refused a gradual reduction of their dry body weight. In the remaining 21 patients, the weight reduction was associated with a decrease in cGMP levels in all cases and with a decrease in ANP levels in all but two cases. Fourteen of the 21 patients reached a cGMP level below 20 pmol/mL after weight reduction, and at that time, none of these showed signs of pulmonary congestion on chest x-ray. All seven patients, whose cGMP levels remained above 20 pmol/mL despite the reduction, had documented heart disease with impairment of left ventricular function. These results suggest that the plasma cGMP level after hemodialysis is more apt for the determination of dry body weight than is ANP or a chest roentgenogram.

The postdialytic plasma level of cGMP, a marker for the release of atrial natriuretic peptide (ANP) in humans, is closely related to hypervolemia in chronic hemodialysis patients. In order to test the practicability of routine postdialysis cGMP determination for the detection of fluid overload, ANP and cGMP levels in the total hemodialysis population of 81 patients were measured with blood samples drawn immediately after hemodialysis. Twenty-three patients had a cGMP level of more than 20 pmol/mL. In 13 of these, pulmonary congestion was present on the chest roentgenogram. Two of these patients refused a gradual reduction of their dry body weight. In the remaining 21 patients, the weight reduction was associated with a decrease in cGMP levels in all cases and with a decrease in ANP levels in all but two cases. Fourteen of the 21 patients reached a cGMP level below 20 pmol/mL after weight reduction, and at that time, none of these showed signs of pulmonary congestion on chest x-ray. All seven patients, whose cGMP levels remained above 20 pmol/mL despite the reduction, had documented heart disease with impairment of left ventricular function. These results suggest that the plasma cGMP level after hemodialysis is more apt for the determination of dry body weight than is ANP or a chest roentgenogram.

We investigated whether cGMP might be a suitable marker of ideal weight in chronic haemodialysis patients. In 20 patients on chronic haemodialysis (10 males, 10 females, mean age 55.5 +/- 7.4 years; mean interdialytic weight gain 2.4 +/- 1.1 kg) we determined plasma ANP and cGMP values before and after several haemodialysis treatments. ANP and cGMP before haemodialysis were markedly elevated (ANP 255 +/- 190 pg/ml; cGMP 28.6 +/- 16.2 pmol/ml). A significant decrease was found after haemodialysis (ANP 169 +/- 88 pg/ml; cGMP 13.5 +/- 7.4 pmol/ml). These values were still well above normal. There was a significant positive correlation between excessive body-weight delta P (difference between actual weight and estimated ideal weight), indicating fluid overload and ANP before (r = 0.57; P less than 0.001) and after haemodialysis (r = 0.47; P less than 0.001) as well as cGMP before (r = 0.42; P less than 0.01) and after haemodialysis (r = 0.85; P less than 0.0001). With cGMP and delta P after haemodialysis, the correlation appeared to be close enough for clinical application. All patients with a cGMP value of 18 pmol/ml or more after haemodialysis had an excessive body-weight of at least 0.5 kg. We conclude from these data that the plasma cGMP value determined immediately after haemodialysis is a sensitive marker for hyperhydration in patients with end-stage renal disease.

Thirty-seven patients with volume-retaining disorders (liver cirrhosis with ascites,n=8; heart failure NYHA III–IV,n=12; endstage renal failure,n=17) and twelve healthy age-matched controls were given a small dose (33 μg) of hANF (human atrial natriuretic factor). We tested the resulting hemodynamic and renal effects as well as the effect on plasma cyclic GMP levels and compared them with the properties of platelet ANF receptors. The ANF injection evoked an increase in cyclic GMP plasma levels of 19.3±2.2 nM in healthy controls. This increase tended to be smaller in the cirrhosis group (15.5±3.3 nM) and in the heart failure group (16.8±2.3 nM) than in the dialysis group (20.5±2.5 nM). The invasion rates of cyclic GMP were comparable in all groups, but the evasion rates increased more in the heart failure and endstage renal failure groups (27.9±7.7 min and 26.1±3.4 min, respectively) than in the cirrhosis and control groups (14.9±1.9 min and 14.2±1.9 min, respectively). Patients with endstage renal failure and congestive heart failure showed a smaller decrease in diastolic blood pressure than controls and patients with liver cirrhosis. Renal actions of ANF were diminished in cirrhosis and heart failure patients. Binding capacities of platelet ANF receptors were higher in the control group (12.2±1.5 receptors/cell) than in the patient groups (cirrhosis, 7.8±1.2; endstage renal failure, 8.0±0.9; heart insufficiency, 8.0±1.0 receptors/ cell), with no differences among the patient groups. Binding affinities were not significantly different. Correlation analysis showed that the relationship between the actions of ANF and the increases in plasma cyclic GMP levels is loose and cannot predict the hemodynamic or renal effects of exogenous ANF in a given patient. Although the behavior of plasma cyclic GMP levels fails to predict the responsiveness of the body to ANF in a given patient, it does reflect the differences between the patient groups and the control group. In contrast, we found no correlation between the properties of platelet ANF receptors and ANF action.