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Biomedical subjects

N Gretz

Publications and source records attributed to N Gretz.

138 records · Page 8Linked to original sources

Low-protein diet supplemented by keto acids in chronic renal failure: a prospective controlled study.

In this prospective controlled study, a 30-g protein-restricted diet supplemented by keto acids resulted in a delayed rate of progression of chronic renal failure. The effect of this treatment differed according to the underlying renal disease. The rate of progression of chronic renal failure was delayed by a factor of at least 2. A need for long-term observations to quantify the effectiveness of this therapy is shown. A new pragmatic approach to the evaluation of long-term studies in patients with chronic renal failure is demonstrated.

Clinical Trials as Topic↗

Predictability of the progression of chronic renal failure.

The progression of chronic renal failure has been claimed to be predictable by means of mathematical models. The present study assesses, in 110 adult patients, the prediction error caused by the application of these models. The study shows that the prediction error has a wide range, which indicates that these models should be used with caution for prediction purposes in individual patients. Improvements of the models are proposed, and a new approach is demonstrated.

Adult↗

Survival time in cystinosis. A collaborative study.

In a retrospective study the overall survival time of 205 cystinotic patients of six countries was determined. The median survival time was 8.5 years. The median time for 'renal death' (age at death due to uraemia or age at starting renal replacement therapy) was 9.2 years. The youngest patient dying of renal death was 5.2 years. No sex difference in survival time was noticed. Furthermore no difference in survival time was noted between the different countries. The analysis of the overall survival curve indicates no clear differences between the infantile and adolescent types of cystinosis.

Adolescent↗

A new in vitro bioassay for cyst formation by renal cells from an autosomal dominant rat model of polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent human inherited diseases. The main feature of the disease is the development of renal cysts, first occurring in the proximal tubules, and with time, dominating all segments of the nephron, leading to end-stage renal disease in 50% of the patients in their fifth decade of life. A therapy for polycystic kidney disease (PKD) has not yet been developed. Patients coming to end-stage ADPKD require long-term dialysis and/or transplantation. A suitable animal model to study ADPKD is the spontaneously mutated Han:SPRD (cy/+) rat, but a method to cultivate Han:SPRD (cy/+) derived renal cells which preserves their ability to form cyst-like structures in vitro has previously not been reported. Based on this well-characterized animal model, we developed a cell culture model of renal cyst formation in vitro. When renal cells of the Han:SPRD (cy/+) rat were isolated and cultured under conditions that prevent cell-substratum adhesion, large amounts of cyst-like structures were formed de novo from Han:SPRD (cy/+) derived renal cells, but only a few from control rat renal cells. In contrast, when cultivated on plastic as monolayer cultures, Han:SPRD (cy/+)-derived and control rat-derived renal cells were indistinguishable and did not form cyst-like structures. Immunohistochemical characterization of the cyst-like structures suggests tubular epithelial origin of the cyst-forming cells. The amount of cysts formed from Han:SPRD (cy/+)-derived renal cells grown in a stationary suspension culture is susceptible to modulation by different conditions. Human cyst fluid and epidermal growth factor both stimulated the formation of cysts from Han:SPRD (cy/+)-derived renal cells whereas taxol inhibited cystogenesis. In contrast, neither human cyst fluid nor epidermal growth factor affected the amount of cysts formed by control rat renal cells. As the culture model reported here allows not only the distinction of PKD-derived tubular epithelium from its normal counterpart, but also the modulation of cyst formation especially by Han:SPRD (cy/+)-derived renal cells, it might be a useful prescreening protocol for potential treatments for PKD and thus reduce the need for animal experiments.

Animals↗

Creatinine clearance, Cockcroft-Gault formula and cystatin C: estimators of true glomerular filtration rate in the elderly?

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.

Aged↗

Focal overexpression of collagen IV characterizes the initiation of epithelial changes in polycystic kidney disease.

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.

Animals↗