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Aims: To evaluate the quality of bedside estimation of glomerular filtration rate (GFR) in hospitalized elderly patients., Methods: We evaluated common estimators of GFR in 29 women and 32 men aged 60 and older hospitalized in a geriatric ward: creatinine clearance (CCR), the Cockcroft-Gault formula (CG), the modification of diet in renal disease formula (MDRD), Baracskay formula (BAR), and a newly developed formula derived recently by us (GCM). Inulin clearance (CINU) was used to assess GFR. Exclusion criteria were mental illness and urinary incontinence., Results: According to Bland and Altman accuracy and precision of all estimators were low and there was an underestimation of actual GFR: CCR 38.9 ml/min; CG 39.7 ml/min; MDRD 19.8 ml/min; BAR 34.0 ml/min, and GCM: 24.7 ml/min. The accuracy and precision of all methods were even lower in patients with a GFR of >90 ml/min and in patients with diabetes. In receiver-operating characteristics (ROC analysis) all formulas were superior to serum creatinine and overall MDRD disclosed the best results in detecting both a GFR of <90 ml/min and <60 ml/min., Conclusions: In general, estimation errors are large in an acute care setting. However, formula estimation is clearly superior to serum creatinine and CCR. MDRD gave the best results but may be replaced by the more simple CG and GCM formulas, whereas BAR was inferior.

Background: The aim of this study was to assess the accuracy and precision of estimators of true glomerular filtration rate (GFR) (Cockcroft formula, measured creatinine clearance (CCR) and a cystatin-C-based estimation) in elderly patients attending a geriatric department. Additionally, parameters influencing GFR in the elderly were evaluated., Methods: 30 patients aged 57-90 years treated in the Geriatric Department for pulmonary or cerebral diseases were included in the study. Nine patients were diabetic and 16 hypertensive. Exclusion criteria were advanced dementia, acute heart failure and primary renal disease. Inulin clearance (CINU), CCR and estimation by Cockcroft-Gault equation (CG) were performed on the same day. For comparison of the methods an analysis according to Bland and Altman was used, depicting the mean difference between the methods and the limits of agreement of the differences, representing their 95% interval of confidence. Furthermore, the influence of confounding variables on GFR estimation was analyzed by multiple regression., Results: Baseline characteristics showed a median age of 74.5 years and a median body weight of 66.7 kg. Median values for serum creatinine 88.4 micromol/l, 5.74 mmol/l for urea and 1.57 mg/l for cystatin C. CCR (median: 51.6 ml/min) and CG (median: 63.0 ml/min) underestimated CINU (median: 83.3 ml/min). Both methods showed poor precision compared with CINU. The upper limit of agreement of the difference was 101.3 ml/min for CCR and 81.4 ml/min for CG, the lower limit was -33.8 ml/min for CCR and -24.6 ml/min for CG. Among frequently used variables to predict GFR, the reciprocal of serum creatinine and body weight revealed a significant influence but not age or gender. A cystatin-C-based estimation of GFR, derived from regression analysis, did not improve the precision of the estimation of GFR compared to CG. Additionally, the occurrence of diabetes mellitus disclosed a borderline influence on the estimation of GFR., Conclusion: CCR is not only inconvenient and time consuming, but also imprecise and inaccurate in the elderly, mainly due to reduced muscle mass and erroneous urine sampling. CG and a cystatin-C-based estimation are slightly more adequate, but overall there is no sufficiently precise formula for GFR estimation in the elderly., (Copyright 2002 S. Karger AG, Basel)

Severe podocyte damage including detachment from the GBM leads to adhesion of the glomerular tuft to Bowman's capsule, thus to a local loss of the separation of the tuft from the interstitium. Perfused capillaries contained in the tuft adhesion deliver their filtrate no longer into Bowman's space but into the interstitium. In response, interstitial fibroblasts create a cellular cover around the focus of misdirected filtration, interpreted teleologically, aiming at preventing the entry of this fluid into the interstitium. This results in the formation of a crescent-shaped, fluid-filled paraglomerular space overarching the segmental glomerular lesion. Extension of this space over the entire glomerulus leads to global sclerosis; extension of this space via the urinary pole onto the outer aspect of the corresponding tubule leads to the degeneration of the tubule. Since, as we postulate, such misdirected filtration and filtrate spreading is the crucial mechanism of damage progression in 'classic' focal segmental glomerulosclerosis (FSGS), the most characteristic structural injury of FSGS is the merger of the tuft with the interstitium, represented by a tuft adhesion, later a synechia. Therefore, histopathologically, 'classic' FSGS is best defined by an adhesion/synechia of the tuft to Bowman's capsule.

The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.

Exposure to complement-activating cellulosic dialysis membranes has been claimed to adversely affect the course of acute renal failure. To test this hypothesis, male Sprague-Dawley rats were allocated to two groups: in group I, acute renal failure was induced by bilateral renal artery clamping, while group II animals underwent a sham procedure. In each group, the rats were further allocated to undergo hemodialysis with either a Cuprophan, a Hemophan, or a PAN miniDialyzer membrane 3 and 7 days after surgery or no dialysis. The renal function was measured by inulin clearance on the days following dialysis. Temporary occlusion of the renal arteries led to a rapid increase in serum urea and creatinine levels that peaked between 24 and 48 h after surgery and declined slowly thereafter. Peak urea values were similar in the acute renal failure groups. The hemodialysis sessions were well tolerated. Degree and rate of recovery were similar in all acute renal failure groups irrespective of whether they underwent dialysis or not or the type of the dialysis membrane. Complete recovery was observed in all the acute renal failure groups by the end of the observation period. Our findings refute the hypothesis that in ischemic acute renal failure exposure to complement-activating cellulosic dialysis membranes impairs the recovery of renal function.

Changes of extracellular matrix are involved in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The relationship between epithelial changes and extracellular matrix production was studied in a new rat model (Han:SPRD/cy+) at an early phase of cystogenesis. Messenger RNA expression of the alpha 1(IV)-chain of collagen type IV, the main structural component of basement membrane, was localized by in situ hybridization. The presence of collagen IV-protein was shown by immunohistochemistry. At an initial stage, cysts were lined with normal-appearing epithelium except for focal zones of less differentiated cells exhibiting strong collagen alpha 1(IV) mRNA expression and a thickened basement membrane. In these zones, an increase in cell number (2.39-fold) per unit epithelial area indicated hyperplastic growth. Conspicuously, these zones were found at 'bottleneck'-like transitions from normal-size tubules to cystic expansions. Intermediate stages of cysts showed more prominent extracellular matrix deposits and an overall maximally enhanced collagen IV mRNA expression, whereas terminal stages were lined with a flat, simplified epithelium and exhibited moderate collagen IV expression. We suggest that focally enhanced expression of collagen IV in the tubular epithelium and surrounding interstitium of Han:SPRD/cy+ rat kidney is initially involved in cyst development.

Unlabelled: Recently, the existence of a rat strain exhibiting autosomal dominant polycystic kidney disease (PKD) resembling human PKD has been described. An exact description of the course of chronic renal failure in this strain, however, is still missing. Thus the aim of this study was to analyze the long-term course of renal failure in these rats. In addition, unilateral nephrectomy (UNX) was performed in order to evaluate the impact of UNX on the occurrence of uremia. Our data clearly revealed that 70-80% of all animals of this rat strain developed uremia within 21 months. Additionally, proteinuria and hypercholesterolemia occurred, while the blood pressure was fairly unaffected. Also a slight degree of anemia was noted. In this long-term study death was due to uremia. The median survival time was significantly shorter in UNX PKD (median 11.6 months) than in non-UNX PKD animals (17.0 months; log-rank test: p = 0.001)., In Conclusion: with respect to renal function this rat model resembles human PKD disease. Furthermore, we could demonstrate that UNX is suitable to accelerate the rate of progression of renal failure in this model.

Metabolic acidosis is a common finding in uremia. The metabolic consequences, however, are poorly understood. Thus, the aim of our study was to assess the effect of chronic metabolic acidosis in 5/6-nephrectomized male Sprague-Dawley rats given a normal (18%; n = 19) and a low-protein diet (8%; n = 23). Each of these groups was sequentially given CaCO3 and CaCl2 in the drinking water for a fortnight each. The animals were randomly assigned to start either with CaCO3 or CaCl2 (random cross-over design). The blood pH decreased significantly in both CaCl2 groups (18% protein: CaCO3 7.18 vs. CaCl2 7.11; 8% protein: CaCO3 7.26 vs. CaCl2 7.09) as did standardized base excess (18% protein: CaCO3-5.9 vs. CaCl2-9.7; 8% protein: CaCO3-3.6 vs. CaCl2-12.6). Food intake declined during acidosis in both groups, but more in the 18% protein group. The same occurred with body weight (g) in the 18% group, which decreased dramatically (8% protein: CaCO3 389 vs. CaCl2 390; 18% protein: CaCO3 413 vs. CaCl2 366). The change in body weight was reflected in the urinary urea excretion (mg/24 h/g food) (8% protein: CaCO3 0.9 vs. CaCl2 1.0; 18% protein: CaCO3 2.2 vs. CaCl2 30.8). There was a significant increase in proteinuria (mg/24 h) in the 8% group (CaCO3 10 vs. CaCl2 15), while in the 18% group no real change occurred (CaCO3 24 vs. CaCl2 18). Factoring the proteinuria for food intake, however, also resulted in a tendency towards an increased proteinuria in the 18% group.(ABSTRACT TRUNCATED AT 250 WORDS)

In 12 male 5/6 nephrectomized Sprague-Dawley rats we analyzed the influence of commercially available amino/keto acid supplements on proteinuria. The addition of different supplements to an 8% protein diet resulted in an increase of preexisting proteinuria. Keto acids per se do not seem to cause a remarkable degree of proteinuria/hyperfiltration. Our data underline the importance of the protein content of a low-protein diet and the composition of amino/keto acid supplements, as these factors per se can cause hyperfiltration and might accelerate progression of chronic renal failure.

Protein-calorie malnutrition (PCMN) in patients suffering from chronic renal failure treated with a low-protein diet (LDP) is generally considered to be the major adverse effect of such a diet. One cause of PCMN might be that these protein-restricted diets do not supply enough energy, although all of them are supposed to provide at least 35 kcal/kg body weight (BW). In order to test this hypothesis, we analyzed the hypothetical protein and energy intake of a patient on different LPDs. The food intake of such a patient was simulated by analyzing the average composition of 28 complete daily menus. The daily menus simulating 9 dietary schedules (0.3 g protein/kg BW; n = 6; 0.6 g protein/kg BW; n = 3) were taken from 5 different German cookery books. Our analysis revealed that only 2 schedules supplied enough energy. All others were deficient in energy by about 500 kcal/day. The deficiency occurred to the same extent in schedules for diets providing 0.3 and 0.6 g of protein/day. Therefore we conclude that PCMN in patients on LPDs is often due to an insufficient energy supply. The use of less protein-restricted diets does not necessarily prevent PCMN, as also these diets may be low in calories. Thus the use of caloric supplements, e.g. wine or polysaccharides, and correct dietary counseling by a skilled dietitian are recommended.

In 12 male 5/6 nephrectomized Sprague-Dawley rats we analyzed the influence of commercially available amino/keto acid supplements on creatinine clearance. The addition of different supplements to an 8% protein diet resulted in an increase of creatinine clearance. Keto acids per se do not seem to cause a remarkable increase in creatinine clearance/hyperfiltration. Our data underline the importance of the protein content of a low-protein diet and the composition of amino/keto acid supplements, as these factors per se can cause hyperfiltration and might accelerate progression of chronic renal failure.

The data presented demonstrate that the underlying renal disease and the type of diet used are considerably influencing the rate of progression of chronic renal failure. In relative terms the course of the renal disease is mostly changed in patients suffering from glomerulonephritis, while in absolute terms patients suffering from polycystic kidney disease exhibit the slowest rate of progression. The comparison suggests that a low-protein diet purely based on vegetarian food might considerably slow down the overall rate of progression of chronic renal failure. This finding is supported by results obtained in animal experiments.

As a new method for the analysis of proteinuria isoelectricfocusing with immobilized pH gradients is introduced. Ths new approach has several advantages over the conventional methods. The applicability is demonstrated by analysing the long-term changes in proteinuria of a 5/6 nephrectomized rat. Soon after 5/6 nephrectomy, a glomerular pattern of protein excretion predominates which later on is followed by a tubular pattern.