Middle molecules in patients with pre-dialysis chronic renal failure: a comparative clearance study.

Residual renal function is an important parameter int he design of dialysis regimens. In this study residual renal clearance of potential uremic toxins in the middle molecular weight range (originally thought to be 300-2000 daltons, but now considered close to 300-700 daltons) was investigated in patients with predialysis chronic renal failure. Middle molecules were isolated from uremic sera and urines by gel filtration and further separated by gradient elution chromatography to give 7 to 8 definable uremic middle molecular weight species. The renal clearances of middle molecule fractions were compared with simultaneously measured endogenous creatinine, urinary inulin and single short inulin clearance. The four middle molecule fractions which were quantitated (7a, b, c and d) were found to be freely filtered and to have renal clearances in end stage renal failure approximately equal to the endogenous creatinine clearance. Thus, renal handling of middle molecules is strikingly different from that of other peptides of peptide hormones in that the species do not appear to be catabolized, secreted or reabsorbed by the renal tubules to any significant degree.

Haemodynamic effects of prenalterol in patients on dialysis.

Haemodialysis hypotension occurs with particular frequency in bilateral nephrectomised patients. This reflects the importance of the renin-angiotensin-aldosterone system for maintaining normal blood pressure. Failure of vascular access (due to clotting and thrombosis of shunts) and ischaemic necrosis of transplanted kidneys in hypotensive patients prompted us to treat them orally with a new beta 1-adrenergic agent (prenalterol). Blood pressure was normalised in 4 out of 5 patients. Because of delayed renal elimination of the drug, daily dosage must be reduced to prevent symptoms of adrenergic stimulation. A study of the pharmacokinetics of prenalterol in uraemia is in preparation.

Renal handling of middle molecules in uremic patients and in the isolated rat kidney.

Renal handling of uremic middle molecules (MW 300-2000 daltons) was investigated (1) in the diseased kidney in nine patients suffering from chronic renal failure in the pre-dialysis phase, and (2) in the isolated perfused rat kidney using hemofiltrate and albumin (5 gm/100 ml) containing perfusate. Middle molecules clearances are compared to the simultaneously measured inulin and creatinine clearances. Four middle molecule fractions (peak 7a, 7b, 7c, and 7d) were quantitated after high-speed gel filtration and gradient elution chromatography and found to be freely filtered (= middle molecules clearances not differing from inulin and creatinine clearances) in uremia in man. In the "intact" (isolated perfused) rat kidney, elimination also takes place by glomerular filtration (peak 7a, 7c at high perfusate levels). Peaks 7b and 7d are slightly reabsorbed (15% and 25%, respectively, of filtered load), whereas 7c1 is secreted up to 220% of inulin clearance at low perfusate levels. No renal catabolism and high urinary excretion of middle molecules clearly indicate different renal handling of this species in comparison to other peptides or peptide hormones of the same molecular weight range.

[On the clinical value of roentgenological observation of the clinical course of renal osteopathy (author's transl)]. / Zum klinischen Wert röntgenologischer Verlaufsbeobachtungen bei renaler Osteopathie.

Basing on radiological observation of the course of renal osteopathy confirmed both clinically and by bone biopsy in 96 patients -- the x-ray examination comprising primarily the entire axial skeleton including the proximal extremities and hands -- 60% of the patients showed mineralisation in their hands. The rest of the skeleton was affected only if there were identifiable alterations at the hands, although the affection of the axial skeleton was definitely lower in terms of percentage. Hence, radiological observation of renal osteopathy based on x-ray films of both hands with additional magnification technique appears both possible and meaningful.

Angiographic results in interstitial, vascular and glomerular kidney diseases.

In earlier stages of parenchymal kidney diseases different changes are to be seen in angiography. No single sign appeared to be pathognomonic for glomerular nephritis, vascular disease or interstitial nephropathy. But the disproportionate frequency of some angiographic features assumed discriminatory value. Morphometry of the renal arteriograms discriminated statistically significant interstitial, vascular and glomerular diseases. The correct angiographical diagnosis was made in 76%.

Kinetics of PTH metabolism and PTH fragments in chronic renal failure.

Distribution and metabolic degradation of bPTH was studied in man after infusion of 400 U bPTH and blood sampling up to 2h. Disappearance rates of intact 1-84 bPTH, carboxyl- and amino-regional peptides were calculated for healthy subjects (n = 12); patients suffering from moderate (GFR 15--30 ml/min, n = 4) and advanced (GFR less than or equal to 10 ml/min, n = 36) chronic renal failure; and bilateral nephrectomized patients (n = 3). Two components with a rapid and a slow disappearance rate can be separated ("distribution", "metabolism"). Half-lives are found to be in the range known from animal experiments with marked differences between intact 1-84 PTH and peptide fragments. Influence of impaired renal function on metabolic turnover rates of PTH is given.