[Renal clearance of hippurate in persons with chronic renal insufficiency]. / Ledvinová clearance hipurátu u jedincu s chronickou renální insuficiencí.

In 8 subjects with chronic renal failure treated conservatively the renal hippurate clearance (CHip), polyfructosan (CPF) and creatinine (Ccr) clearance was assessed. The mean values of the investigated variables were as follows: CHip = 1.06 +/- 0.79 ml/s, CPF = 0.15 +/- 0.08 ml/s, Ccr = 0.27 +/- 0.17 ml/s. The ratios between the investigated clearance values were: CHip/CPF = 6.9 +/- 4.2 and CHip/Ccr = 4.2 +/- 1.4. The ratio of CHip/CPF was in some instances as high as 10 or more. Between values of CHip/CPF and the plasma hippurate concentration (PHip) a significant negative (non-linear correlation was found (p < 0.01). When the PHip values were very high, the value of the CHip/CPF ratio was close to 1. The recorded findings confirm that in subjects with chronic renal failure in the residual nephrons hippurate is synthetized and its urinary excretion in relation to glomerular filtration is increased. The findings suggest also that in these patients the tubular transport for hippurate is saturated. It will be necessary to take into account the possible saturation of tubular transport for hippurate when interpreting changes of drug excretion (i.e. those excreted by the same mechanism as hippurate) in subjects with chronic renal failure.

[Renal excretion of amino acids in patients on a regular dialysis program]. / Renální vylucování aminokyselin u nemocných v pravidelném dialyzacním programu.

In 10 patients with chronic renal failure and a polyfructosan S clearance (CPFS): 1.91-12.70 ml/min (mean 5.68 ml/min) with a preserved residual diuresis (more than 1000 ml/24 hours) renal excretion of 22 amino acids by residual nephrons was investigated before and 12 hours after haemodialysis. It was revealed that 12 hours after haemodialysis a significant drop of the filtered amount of all investigated amino acids occurred. Renal clearance of Ser, Pro, Glu, Gly, Ala, Tyr, Met, Leu and Cit after haemodialysis declined significantly (p < 0.05-0.001). Haemodialysis was not associated with significant changes of fractionated excretions (FE) of amino acids with the exception of Gly (p < 0.01) and Trp (p < 0.05) where an increase of FE was recorded. Hitherto assembled results are consistent with the idea that a reduction of the tubular resorption of amino acids in the residual nephrons in subjects with chronic renal failure cannot be explained by a change of their filtered amount (as "overflow" aminoaciduria) nor as the consequence of retention of some dialyzable substances which could inhibit tubular transport of amino acids. The reduced tubular transport of some of the investigated amino acids (Cys, Lys, Cit, Met, Asn+Gln, Orn, Ile) was significantly related with the drop of tubular sodium transport.

[Relation between creatinine clearance and glomerular filtration in various stages of chronic renal disease]. / Vztah mezi klerancí kreatininu a glomerulární filtrací v ruzných stadiích chronického renálního onemocnení.

The relationship between creatinine clearance (Ccr) and inulin (C(in)) was investigated in 20 healthy subjects (group A) and 54 subjects with chronic renal disease (C(in): 10-80 ml/min/1.73 m2) treated conservatively (group B) and in 10 subjects with regular dialyzation treatment and a preserved residual diuresis (more than 1000 ml/24 h) (group C). In subjects from group B the Ccr/C(in) values were significantly higher than in healthy subjects (p < 0.01). In subjects of group C the values of Ccr/C(in) before dialysis did not differ significantly from values recorded in healthy subjects. Twelve hours after dialysis a marked increase of C(in)/Ccr occurred (p < 0.001). The findings are consistent with the idea that the increase of tubular creatinine secretion in patients with chronic renal disease is associated with a rise of its plasma concentration. In terminal stages in chronic renal failure there is, however, again a drop of tubular creatinine secretion which is reversible and rises after dialysis. These changes in tubular creatinine secretion could be explained by the fact that in chronic renal failure substances cumulate in the organism which inhibit tubular creatinine secretion. Due to haemodialysis the concentration of these inhibitors of creatinine secretion declines and after dialysis this process increases again temporarily. The findings suggest that the residual Ccr value assessed before dialysis is closer to the real value of glomerular filtration than values assessed during dialysis.

[Evaluation of glomerular filtration in patients after renal transplantation and treatment with cyclosporin A]. / Hodnocení glomerulární filtrace u nemocných po transplantaci ledviny lécených cyklosporinem A.

According to some findings (Ross et al. 1987) the creatinine plasma concentration (Pcr) is an inaccurate indicator of glomerular filtration (GFR) in patients with a transplanted kidney, treated with cyclosporin A (CyA), who are in a stabilized state of renal function. In the submitted work the authors investigated whether the inaccuracy of the assessed GFR based on Pcr or creatinine clearance (Ccr) is greater than in patients with various chronic renal diseases who at the time of examination did not take any drugs. The investigation was made in 30 patients with a transplanted kidney treated with CyA as well as azathioprine and prednisone. The authors examined also 51 patients with various chronic renal diseases, mostly chronic glomerulonephritis or tubulo-interstitial nephritis. The GFR value was assessed on the basis of polyfructosan clearance (CPF). In subjects with a transplanted kidney a significant linear relationship was found between Ccr and CPF (r = 0.829, p < 0.001). A similar relationship was found in patients with chronic renal disease (r = 0.935, p < 0.001). The regression lines characterize this relationship in both groups and do not differ significantly. Between values of Pcr and CPF a significant relationship of a hyperbolic character was found in both groups (r = 0.693, p < 0.001 and r = 0.741, p < 0.001 resp.). The hyperbolic relations found in the examined groups did not differ significantly. The findings confirm that a normal or only slightly elevated Pcr value can be associated with a markedly reduced GFR, in some instances to as much as one third of the normal values.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine A treatment and evaluation of glomerular filtration rate in patients with a transplanted kidney.

According to some findings [Ross et al. 1987], the plasma concentration of creatinine (Pcr) is an inaccurate reflection of the glomerular filtration rate (GFR) in renal graft recipients with stabilized renal function, treated with cyclosporine A (CyA). In this study, we sought to determine whether the inaccuracy of GFR assessment on the basis of Pcr or creatinine clearance (Ccr) in these individuals is greater than in patients suffering from various chronic renal diseases untreated by any drugs during the examination. The study was performed in 30 renal graft recipients, treated with CyA in combination with azathioprine and prednisone. Further, 51 patients suffering from a chronic renal disease, mostly chronic glomerulonephritis or tubulointerstitial nephritis, were investigated. GFR was evaluated on the basis of polyfructosan clearance (CPF). A significant linear relation between Ccr and CPF (r = 0.829, p less than 0.001) was demonstrated in individuals with a transplanted kidney graft treated with CyA. A relationship of the same character was observed in the group of patients suffering from chronic renal diseases (r = 0.935, p less than 0.001). There is no statistically significant difference between the regression lines characterizing these relationships in both groups. A significant correlation of hyperbolic character between Pcr and CPF was found in both groups investigated (r = 0.693, p less than 0.001, and r = 0.741, p less than 0.001, respectively). The hyperbolic relationship noted in the studied groups did not differ significantly. These findings confirm a normal, or a mildly raised Pcr can be associated with a marked decrease in GFR, in some cases to a value as low as a third of the normal one.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of hemodialysis on potassium excretion by residual nephrons]. / Vliv hemodialýzy na vylucov ání draslíku reziduálními nefrony.

In 19 patients with chronic renal failure and still preserved residual diuresis the inulin clearance (Cin) and renal potassium excretion were assessed before and 12 hours after haemodialysis (HD), combined with conventional ultrafiltration. The mean value of Cin after HD declined significantly (p less than 0.001). As a result of HD a significant decline of the plasma potassium concentration occurred (p less than 0.005) and of the urinary excretion (p less than 0.01). The mean value of the fractional potassium excretion (FEK) did not change significantly as a result of HD. The reduced urinary K excretion after HD correlated significantly (p less than 0.05) with the decline of Cin. The findings suggest that the decline of the urinary potassium excretion after HD is above all due to a decline of the glomerular filtration rate. The tubular potassium secretion does not change significantly under these conditions. These findings support indirectly the idea that the increased tubular potassium secretion in residual nephrons in patients with chronic renal failure is not conditioned by retention of low-molecular dialysable substances.

[The critical value of residual kidney function in patients with chronic kidney failure from the viewpoint of the concentration of urea and potassium in the plasma]. / Kriticheskaia velichina ostatochnoi funktsii pochek u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu s tochki zreniia kontsentratsii mocheviny i kaliia v plazme.

Residual kidney function was examined in 10 patients with chronic renal insufficiency under balance conditions and in 30 outpatients on the basis of urea clearance (Curea) and potassium clearance (CK). Protein intake was 35-40 g/day (0.5 g/kg/day) and potassium intake was 30-40 mmol/day. Under these conditions the critical values of residual kidney function were as follows: 1) plasma urea concentration (Purea) did not exceed 30 mmol/l if Curea did not drop below 3.8 ml/min; 2) plasma potassium concentration (PK) did not exceed 5 mmol/l if CK did not decrease below 4.1 ml/min. Clinical examination of Curea and CK provides additional information to the examination of creatinine clearance (Ccr) or its plasma concentration (Pcr). Our results suggest that the critical value of residual kidney function cannot be defined only on the basis of examination of Ccr or Pcr. Examination of Curea and CK can help in the interpretation of very high Purea and hyperkalemia in patients with chronic renal insufficiency.

Renal amino acid excretion and aging.

The urinary excretion and serum concentration of amino acids were studied in 62 healthy individuals aged 15 to 70 years. In elderly subjects (61-70 years), it was found that renal amino acid clearance per 100 ml GFR (fractional excretion, FE) rose significantly in the following amino acids: CYS, VAL, MET, ILE and LEU. Since the serum concentrations of these amino acids showed no significant changes, but the GFR was reduced, it can be concluded that the raised FE of these amino acids was due to a decrease in their effective tubular reabsorption. A significant correlation was found between FENa and FE of most amino acids including those mentioned above. The findings support the assumption that changes in tubular Na+ transport probably participate in the changes of tubular amino acid transport in elderly individuals.

[Metabolic characteristics of patients with chronic renal failure in long-term diet therapy and substitution with keto analogs of essential amino acids]. / Stoffwechselverhalten bei Patienten mit chronischer Niereninsuffizienz unter diätetischer Langzeittherapie und Substitution mit Ketoanalogen essentieller Aminosäuren.

12 patients suffering from chronic renal failure did receive for 12 to 22 months a special protein-poor diet containing 20 g of high-class proteins and essential amino acids (4.8 g/d). During this period the serum levels of albumin, transferrin, immunoglobulins, hemoglobin and ferritin did remain unchanged, whereas the levels of C3 was reduced significantly. The glucose metabolism and the serum levels of cholesterol and triglycerids were constant. The results show no metabolic changes during long-term protein-poor diet containing minimal doses of essential amino acids.

[Electrolyte disorders in cadaveric kidney donors before explantation and the functional development of the transplant in the early postoperative period]. / Elektrolytstörungen bei Leichennierenspendern vor der Entnahme und die Funktionsentwicklung des Transplantates in der frühen postoperativen Periode.

In a group of cadaveric kidney transplantations the problem of the dependence of the functional development of the graft on the function of donor kidney before explanation and on the total time of ischaemia in the immediate postoperative period was investigated. Based on the plasma concentration of endogenous creatinine (PKr), urea (PUrea) and the total ischaemic time (GI), the early function of the graft cannot be predicted. On the contrary, the values of PKr, GI and the kidney index (NIKI = PKr x GI) allow an accurate prediction that the early function of the graft will not be sufficient. Early function of the graft is not likely to develop when PKr is higher than 160 mumol/l, total ischaemic time is longer than 30 hours and the NIKI is over 3,500. Severe alterations in the level of serum potassium (SK) occurred in 61.4% of the donors. In cases where SK was 3.0 mmol/l or less, early function of the graft did not develop in 82.3%. With high probability haemodialysis was necessary. More pronounced alterations of the level of SNa occurred in more than 60% of the donors. When SNa was 125 mmol/l or less, early function of the graft did not develop in 76%. Diuresis over 400 ml/h increased significantly the number of early nonfunctional grafts. In cases where fractional sodium excretion (FENa) was over 5%, early function of the graft did not develop. With a FENa less or equal to 1%, early function of the graft was most likely to develop.

The effect of haemodialysis on tubular secretion of creatinine in residual nephrons.

In a group of 16 patients on regular haemodialysis treatment, inulin and creatinine clearance was examined before and 12 h after haemodialysis. Inulin clearance (CIn) decreased significantly (P less than 0.001) whereas creatinine clearance (CCr) did not change after haemodialysis. The CCr/CIn ratio increased significantly (P less than 0.05) as did calculated tubular secretion of creatinine (TCr) (P less than 0.01) and TCr/CIn 100 (P less than 0.001). The results suggest that uraemic sera contain dialysable substance(s) depressing tubular secretion of creatinine.

Residual kidney function and plasma urea concentration in patients with chronic renal failure.

The relationships between the plasma levels of urea (P(urea)), renal clearance of urea (C(urea)) and creatinine (Ccr) at an intake of 0.5 g protein/kg body weight/day were followed in 10 patients with chronic renal failure (CRF) under balance conditions. Under these conditions, P(urea) attained a value of 30 mmol/l when C(urea) had decreased below 3.8 ml/min. By contrast, no correlation could be demonstrated between P(urea) and Ccr under these conditions. The same relationships were followed in another group of 30 outpatients with CRF. Even in patients not followed under balance conditions, C(urea) determination makes it possible to establish whether the high increase in P(urea) is due to the decrease in residual renal function below the critical level or whether extrarenal factors are involved. Likewise, no significant correlation between P(urea) and Ccr could be demonstrated under these conditions. The findings suggest that C(urea) measurement in CRF patients helps to assess residual renal function in terms of P(urea) regulation and provides information that cannot be obtained by Ccr measurement.

[Electrolyte disorders in brain dead organ donors and early functional development of the transplanted kidney]. / Elektrolytové poruchy dárcu orgánu s mozkovou smrtí a casný rozvoj funkce transplantované ledviny.

In 70 cadaverous donors the authors examined 2 hours before collection of organs the serum and urinary electrolyte levels and the creatinine and urea levels. Serious hypokaliaemia (less than 3.0 mmol/l) was found in 24.5% of the donors, hyperkaliaemia (more than 6.0 mmol/l) in 11.4%. Hyponatraemia (less than 125 mmol/l) was present in 11.4%, hypernatraemia (above 160 mmol/l) in 18.6% of the donors. Hyperchloraemia (above 130 mmol/l) was recorded in 22.8 percentage of the donors. In cases where SK less than or equal to 3.0 mmol/l, early functional development of the graft did not occur in 82.3% (p less than 0.001), in cases where SNa less than or equal to 125 mmol/l in 75% (p less than 0.01). When the value of FENa greater than or equal to 5%, early restoration of the graft did not occur in 81.3% of the cases (p less than 0.01). Conversely when FENa less than or equal to 1%, functional development of the graft was highly probable (p less than 0.001). Diuresis above 400 ml/h had an adverse (p less than 0.01) effect on the early functional development of the graft.

Acidification capacity of the kidneys and aging.

The authors studied the acidification capacity of the kidneys in 60 healthy subjects aged 18-70 years after a single load of NH4Cl in a dose of 0.1 g/kg. The acidification load was followed by a significant increase in NH4+ excretion in the first five hours afterwards in young individuals (18-30 years). In subjects aged over 50, changes in NH4+ excretion were nonsignificant under these conditions. Titratable acid excretion rose significantly after the given acidification load in subjects aged 18-60 years; in older subjects it no longer increased significantly. Changes in titratable acid excretion displayed a significant correlation to the renal excretion of phosphates. The findings indicate that the diminished capacity of older subjects to increase titratable acid excretion after an acute NH4Cl load is due to an insufficient decrease in the tubular resorption of phosphates. Renal capacity for adequate reduction of the urine pH after a NH4Cl load was unimpaired.

The plasma concentration and renal elimination of phenols in patients with chronic renal insufficiency.

The plasma concentration and renal elimination of phenols was studied in 32 individuals with various renal insufficiency (CRI) and in 30 healthy subjects. In patients with chronic renal insufficiency the increase in P phenols values correlated directly with Per and P urea. Daily urinary excretion of phenols in patients with CRI is only mildly decreased compared with that in healthy controls. Renal clearance (C phenols), 8.52 (+/- 2.69) ml/min on an average, decreases significantly in patients with CRI. While fraction excretion of phenols (FE phenols) was 9.53 (+/- 4.14) % on an average in healthy persons, patients with CRI displayed a significant increase. A significant linear correlation in the values of FE phenols and FEH2O and those of FE phenols and FE urea was documented. Our findings support the assumption that phenols are excreted by the kidney by a mechanism similar to that of urea excretion. Filtration of phenols in the glomeruli is followed, in healthy volunteers, by their significant reabsorption which is a flow-dependent process. In the residual nephrons of patients with CRI, the tubular reabsorption of phenols is decreased, a mechanism largely compensating the effect of decreased filtration of phenols on their total urinary excretion.

[Long-term administration of a low-protein diet with keto-analogs of essential amino acids and the metabolic status of patients with chronic kidney failure]. / Dlouhodobé podávání nízkobílkovinné diety s ketoanalogy esenciálních aminokyselin a metabolický stav nemocných s chronickým selháním ledvin.

To 12 patients with chronic renal failure (CHRI) for 12-22 months a diet containing 20 g high quality protein supplemented by keto analogues of essential amino acids (KA)--4.8 g/day--was administered. During the investigation period no significant change of the albumin, prealbumin or transferrin level was recorded, nor of Whitehead's quotient, immunoglobulin levels and haemoglobin concentration, serum iron and its binding capacity. However, there was decline of the C3 complement component (p less than 0.01). The investigated parameters of carbohydrate metabolism (fasting blood sugar, immunoreactive insulin, oral glucose tolerance test) did not change, similarly as total cholesterol and triglyceride levels. The originally reduced HDL-cholesterol level increased (p less than 0.05). The achieved results suggest that the long-term administration of a diet with 20 g protein supplemented by the minimal necessary dose of KA does not produce undesirable changes of the investigated metabolic parameters.