Biomedical subjects
Publications and source records attributed to E Ritz.
In patients with renal disease, altered renal function causes elevation of blood pressure, but hypertension in its turn accelerates progression of renal failure. Lowering of blood pressure into the normotensive range is beneficial for slowing progression. Increasing incidence suggests that in this respect ACE inhibitors have unique benefits (renoprotective action).
It has been suggested that frusemide affects plasma parathyroid hormone (PTH) concentrations. To further investigate this issue we analysed plasma intact PTH in 77 patients with chronic renal failure (CCr 8.0-89.8 ml/min per 1.73 m2) as a function of frusemide therapy. The rate of increase of plasma PTH observed with progression of renal failure was faster in patients who received frusemide as compared to patients who did not receive the drug. The slope of the regression line of PTH on CCr was steeper (P less than 0.02) for patients with frusemide (n = 40, slope -0.34) than without frusemide (n = 37, slope -0.20). This effect was specific for frusemide therapy since therapy with other antihypertensive drugs (including thiazides and beta-blockers) was not correlated with PTH plasma concentrations. Frusemide therapy was also associated with a significantly greater urinary calcium excretion in uraemic patients but did not influence other parameters of calcium metabolism. To clarify mechanisms involved in the effect of frusemide on plasma PTH values, seven normal subjects were studied for 24 h before and for 24 h after oral administration of 80 mg frusemide. The main findings were: (1) Median PTH values were higher than on a control day (P less than 0.05) 3 h after frusemide (3.9 pmol/l vs 1.8) and 6 h after frusemide (4.0 vs 2.6); (2) ionised plasma calcium did not change significantly, whereas mean calcium/creatinine ratio increased from 0.20 to 0.46 after frusemide treatment through an increase in absolute calcium excretion; (3) plasma 1 alpha,25-dihydroxyvitamin D3, catecholamines, and magnesium concentrations did not change significantly after frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)
We compared the glomerular filtration rate (GFR) response to amino acids in patients with glomerular disease and polycystic kidney disease. The GFR response to infusion of amino acids (75 g/12 h), of dopamine (2 micrograms/kg per min), or their combination was evaluated in nine healthy probands and in patients with two types of renal diseases at various degrees of renal function: 15 patients with ADPKD and 11 patients with glomerular disease (IgA glomerulonephritis or diabetic nephropathy). Steady-state inulin infusion technique was used. In healthy subjects amino acids increased median C(in) in response to amino acids was not found in glomerular disease. In contrast in most ADPKD patients median C(in) increased after amino acids (+6.0 ml/min; range -4 to +68), (P less than 0.05). The response to amino acids was not modified by dopamine. The results demonstrate that amino acid-induced acute changes of glomerular filtration differ in polycystic kidney disease compared with glomerular disease. These observations may have implications with respect to mechanisms of progression.
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In the following we describe a case of severe hemorrhagic fever with renal syndrome (HFRS) caused by Puumala infection. The diagnosis was made by immunofluorescence technique and by solid phase enzyme immunoassay using recombinant nucleocapsid antigen of a Puumala serotype strain. Such a clinical course with severe bleeding complications is considered untypical for Puumala induced HFRS.
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Absolute or relative deficiency of 1,25(OH)2 vitamin D3 is thought to play a key role in the genesis of secondary (renal) hyperparathyroidism. Elevated concentrations of PTH and--less consistently--diminished concentrations of 1,25(OH)2 vitamin D3 are demonstrable in a considerable proportion of patients with incipient renal failure. Increased PTH concentrations counteract to some extent the trend of 1,25(OH)2 vitamin D3 production to decrease. When iPTH is elevated, prophylactic administration of 1,25(OH)2 vitamin D3 is a logical procedure, even when patients have not yet reached end-stage renal failure. With the use of low doses, the incidence of side effects is low, and excessive lowering of PTH and bone turnover presumably can be avoided. Acute administration of 1,25(OH)2 vitamin D3 to achieve brief episodes of peak plasma levels causes prolonged suppression of pre-pro-PTH mRNA in the parathyroid cell. This provides a rationale to treat symptomatic hyperparathyroidism with intermittent high dose 1,25(OH)2 vitamin D3, either per os or i.v.
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Secondary hyperparathyroidism occurs in the very early stages of renal failure. In the past, there has been considerable controversy concerning the signal triggering secondary hyperparathyroidism. Recently, it has become clear that secondary hyperparathyroidism is, at least to a major extent, the consequence of the deranged endocrine feedback between calcitriol, the secretory product of renal 1-alpha-hydroxylase, and parathyroid hormone. Another recent insight concerns disturbances of the secretion of hypophyseal hormones. These hormones, e.g. GH, gonadotropins and TSH, are secreted in a pulsatile fashion. For all three hormones, reversible abnormalities of secretory rhythmicity have been demonstrated in renal failure. Disturbed oscillatory patterns of hormone secretion provide a new dimension to our understanding of the genesis of endocrine disturbances.
In a cohort of 20 consecutive patients with Wegener's granulomatosis and biopsy-proven pauci-immune crescentic glomerulonephritis three patients were in remission, but developed again a nephritic sediment without signs of systemic disease or positive ANCA titers. The second renal biopsy showed de novo mesangial IgA deposits 6, 17 and 28 months following admission for systemic disease and institution of immunosuppressive treatment. All patients were male, HLA-DR-2 positive and exhibited repeated upper respiratory tract infections. A fourth patient was admitted in end-stage renal failure with high titers of C-ANCA of the IgG isotype and proteinase 3 ab without clinical evidence of systemic manifestations of WG. Renal biopsy showed chronic sclerosing GN with marked IgA deposits. De novo development of IgA-GN is observed in a remarkable proportion of patients with WG and must be distinguished from exacerbation of the systemic disease.
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disorder leading to terminal renal failure. About 8% of the dialysis patients suffer from ADPKD, the gene frequency in the general population being about 1:1000. Many facts contribute to the hypothesis that arterial hypertension plays a major role in the pathophysiology of ADPKD. We observed a prevalence of 30% of hypertension in patients with ADPKD and normal serum-creatinine, and of 80% in patients with terminal renal failure. The time of onset of abnormalities of blood pressure regulation is of great interest, since an increase of blood pressure, even in the normotensive range, accelerates the rate of progression. To answer this question, we examined the time of onset of abnormalities in blood-pressure regulation in 23 probands and 23 control patients in a cross-sectional study. The results document abnormal circadian blood-pressure changes and higher blood pressures, although still within the normotensive range, in asymptomatic carriers of the ADPKD-trait, even before and more definitely after onset of puberty. Even at an age when circadian blood pressure is not significantly different, there is an increased LVM as evidence of target organ damage. The findings suggest that (intermittent) increases in blood pressure and blood-pressure-dependent target organ damage precede overt hypertension and renal failure by years or decades.
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Albuminuria (including the form not detectable by conventional tests, i.e., microalbuminuria) as well as renal dysfunction have recently been recognized as important complications in the patient with essential hypertension. The presence of albuminuria predicts cardiovascular events. Albuminuria is associated with more severe hypertension, with evidence of more advanced target organ damage (e.g., left ventricular hypertrophy), and is more prevalent in high-risk groups (e.g., the elderly). On the other hand, albuminuria may also be associated with generalized endothelial barrier dysfunction and thus predispose to accelerated atherogenesis. Ischemic nephropathy from nonmalignant nephrosclerosis has emerged as an important cause of terminal renal failure in the elderly patient with essential hypertension.
Protein meals and infusion of amino acids cause an increase of glomerular filtration rate in humans and animals with normal renal function despite the circulating renin concentration remaining unchanged. The renal hemodynamic response is not altered by angiotensin converting enzyme inhibitors, but it is obliterated by cyclooxygenase inhibitors. By contrast, chronic exposure to high protein diets raises circulating renin and increases messenger RNA of renin (but not of angiotensinogen) in kidney tissue. Chronically high protein intake raises the glomerular filtration rate and reduces glomerular permselectivity; the reverse is seen with low protein intake. In patients with renal failure, acute amino acid infusion or protein meals cause a paradoxical drop in glomerular filtration rate which is not influenced by converting enzyme inhibitors.
A high frequency of glomerulonephritis (GN) in diabetics, or coexistence of GN with diabetic glomerulosclerosis, has been reported by previous authors, but the true prevalence of GN in diabetics remains to be established. In the Department of Pathology, Heidelberg, from 1.1.1987 to 31.12.1989 we examined all consecutive patients (89 male, 121 female, median age 74 years; 47-98) who came to autopsy with the diagnosis of "diabetes mellitus" to assess this issue in an unbiased sample. Five patients had known type I diabetes, the others type II diabetes or diabetes of unknown classification. In 61/159 patients, proteinuria had been present (no information in 51 patients) and in 99/169 patients renal failure, i.e. serum creatinine above 1.4 mg/dl (no information in 41 patients). Paraffin-embedded kidney specimens from the upper pole of the left kidney were examined by immunohistochemistry (PAP technique; rabbit antihuman IgG; IgM; IgAab). 166/210 of the patients had glomerulosclerosis by light microscopy (129 diffuse, 37 nodular GS). Concomitant glomerulonephritis, i.e. typical mesangial IgA (and IgG) deposits, with mesangial enlargement by light microscopy were detected in only one case. Membranous GN was not found. These findings must be interpreted against the observation of mesangial immune deposits in 6 of 250 consecutive non-diabetic patients who had come to autopsy [Waldherr et al. 1989]. The findings show that an excessive prevalence of undiagnosed glomerulonephritis in our cohort of elderly type II diabetics was not to be found.
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The acute effects of 1,25-Dihydroxy-vitamin D3 [1,25(OH)2D3] on the concentration of cytoplasmic ionized calcium [Ca2+] of cultured rat mesangial cells were studied at the single cell level by microspectrofluorometry of fura-2-loaded cells. Addition of 1,25(OH)2D3 produced an immediate increase of [Ca2]+. This rise in [Ca2+] was sustained and similar to that caused by the Ca2+ channel agonist BAY K 8644. Comparable changes were also observed in cultured human mesangial cells. The effects of the hormone (10 (-10)-10(-7) M) were dose-dependent (62% and 285%). Only 30-40% of the cells responded to stimulation with 1,25(OH)2D3. 25OHD3 also increased Ca2+ whereas 24,25(OH)2D3 and 1aOHD3 were inactive. Addition of 1 mM CoCl2 or 2-5 microM nifedipine largely blocked the effects of 1,25(OH)2D3 suggesting the involvement of Ca2+ channel activation in the rapid 1,25(OH)2D3-induced increase in mesangial cell [Ca2+]. 45Ca uptake studies are consistent with This interpretation.