Impact of age, body mass index, insulin resistance and proteinuria on the kidney function in obese patients with Type 2 diabetes and renal insufficiency.

AIMS: To date, several different equations to predict the glomerular filtration rate (GFR) in patients with renal insufficiency have been developed for different patients groups. Our aim was to determine the prognostic factors of GFR in our homogenous patient group of obese, water-loaded patients with Type 2 diabetes and renal insufficiency, since we assumed that the endogenous creatinine clearance (ECC) alone may not be an accurate method to predict GFR. METHOD: We recruited 46 obese patients (37 men) with Type 2 diabetes and renal insufficiency in our nephrology center in Mettmann (Germany). However, two male patients were excluded from the analysis due to an outlying insulin level or low inulin clearance. The inulin clearance as a measure of renal function performed by the single shot method was compared with the GFR estimated by ECC, Cystatin C, and MDRD formula. Several multiple regression models were built to test the impact of the prognostic factors age, sex, body mass index (BMI), insulin resistance according to the homeostasis model assessment (HOMA), body water (TBW), brain natriuretic peptide (BNP), and proteinuria on the inulin clearance. In the main regression model to predict the inulin clearance by ECC, only the statistically significant prognostic factors of these models were selected, as well as the interaction between GFR predicted by ECC (GFR_ECC) and BMI. RESULTS: The prognostic factors GFR_ECC, age, BMI, HOMA and proteinuria had a statistically significant impact on the inulin clearance (the gold standard of the GFR) in our patient population (p < 0.05). However, the interaction of GFR_ECC and BMI was not significant (p = 0.06) in our model. The model was validated and considered well-fitted with a coefficient of determination (R2) of 0.69. CONCLUSIONS: The independent prognostic factors to determine GFR in obese, water-loaded diabetic patients are GFR_ECC, age, BMI, HOMA and proteinuria. However, our model should be revalidated and tested in a larger sample size to probably detect an interaction between GFR_ECC and BMI as an additional prognostic factor.

[Dialock--an alternative to Permcath and access graft]. / Dialock--eine Alternative zu Permcath und Prothesenshunt.

PURPOSE: An adequate vascular access is the precondition for a well-functioning hemodialysis. Due to the increasing age and the rising co-morbidity of hemodialysis patients the number of those with grafts or central venous catheters (CVC) is steadily growing. The Dialock vascular access system provides a subcutaneously implantable device for hemodialysis that combines the advantages of central venous access with percutaneous puncture. PATIENTS AND METHODS: Over a period of 30 months 26 Dialock vascular access systems were implanted at our department. 17 patients were male, 9 patients female. In 11 patients the implantation of this system was indicated for internal medicine reasons. In 15 long-term hemodialysis patients implantation was carried out as ultimate solution because of persisting vascular access problems. In a comparable control group of 22 hemodialysis patients 47 vascular accesses were registered within the same period. In parallel, another 110 patients with grafts implanted at our department at that time but not put to hemodialysis at our clinic were analysed. RESULTS: In a comparable number of access days the graft and the central venous catheter showed a considerably higher infection rate (Exit site + blood stream infection) per 1,000 hemodialysis access days than the vascular access device. The rate of malfunctions with or without subsequent lysis was higher using the CVC than when applying Dialock or graft. Angiographies with percutaneous transluminal angioplasty (PTA), or thrombectomies, respectively were significantly more often required with the graft than changes of catheter when using the vascular access system. More than half of the 110 patients observed at the same time, who had a graft implanted at our department without subsequent hemodialysis at our clinic had to undergo another surgical or radiologic intervention. CONCLUSION: The Dialock access system represents in our experience a safe and with careful application less complicated vascular access device for the complex hemodialysis patient. With comparatively low infection and complication rates the Dialock vascular access system serves as a good alternative to the permanent CVC (Permcath) as well as to the graft.

Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension.

BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary protein load cause patterns of acute changes in renal function that are fundamentally different from changes in normal controls. METHODS: Renal clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were determined before and after protein ingestion. These tests were performed in healthy controls and in patients with essential hypertension (mean arterial pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period, and after long-term treatment with carvedilol and fosinopril, respectively. RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two-tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16 hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The eight patients who were randomized to receive carvedilol improved in their renal response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min; P=0.04), whereas the eight other patients randomized to receive fosinopril exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the acute shifts in renal plasma flows were not significant. Mean arterial blood pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015). CONCLUSIONS: In essential hypertension an acute protein load induces a decrease in GFR that may normalize under antihypertensive treatment. The acute changes in GFR can be reliably monitored by the here-described compartmental analysis method of renal functional reserve.

System identification of the low-dose kinetics of p-aminohippuric acid.

The renal clearance of p-aminohippuric acid, due to tubular secretion in addition to glomerular filtration, can only be determined by kinetic experiments. Maximal information can be gained from observed temporal marker concentration profiles by fitting dynamic mathematical models of the processes involved, such as absorption, distribution, and elimination, to the kinetic data. Thereby the values of the system constants, such as fractional elimination or fractional distribution rates, and their accuracy measures are determined by methods which are based firstly on measured time-dependent data elicited in an individual test object by perturbing inputs and secondly, on mathematical formulations of prior knowledge of the underlying physiological system. Such methods of model adaptation are called system identification. In this context a computer-based method of system identification and error estimation for the system constants of two-compartment models matched a dynamic concentration profiles of p-aminohippuric acid is presented. The method is used of single-injection experiments to demonstrate that such a technique is able to correctly estimate the clearance of p-aminohippuric acid if sufficiently long experimental protocols are chosen, and to ascertain the sufficient length of a protocol for an individual subject. The renal clearance of p-aminohippuric acid is known to exhibit concentration-dependence generally, but to achieve its maximal value when low doses are applied. The present study deals with the low-dose kinetics of p-aminohippuric acid.

Determination of the glomerular filtration rate by identification of sinistrin kinetics.

A computer-based method of system identification and estimation of parameter variance for two-compartment models matched to dynamic sinistrin concentration profiles for the determination of glomerular filtration rate is described. Thereby a procedure for the judgment of the optimal sampling time horizon is presented. Since single-injection techniques are suspected of yielding systematic overestimation of the glomerular filtration rate, a method is demonstrated confirming that such a technique employing sinistrin kinetics can be used to correctly determine the glomerular filtration rate. The validation of the system parameters gained by the single-injection method is made through prediction of the concentration contour under a constant infusion regimen in the same subject on a different occasion. This was performed in healthy controls and in patients with various degrees of renal insufficiency. Upon consideration of the dependence of the clearance estimates and their variances on the protocol duration in test subjects examined from four to ten hours, an adaptive design of the protocol length is developed.

Tuberculosis of the small bowel with perforation and hematogenous spread in a renal transplant recipient.

A 41-year-old male was admitted because of acute abdomen. A flat plate of the abdomen suggested pneumoperitoneum and a chest X-ray an infiltrate in the right upper lobe. The patient was a renal allograft recipient and was on immunosuppressive therapy with azathioprine, cyclosporine and steroids. At laparatomy inflammatory thickening of the bowel wall was found in the terminal ileum with necrotic areas and two sites of perforation. The involved terminal ileum was removed together with a right hemicolectomy. The resected segment showed exudative ileal tuberculosis and fibrinous and purulent peritonitis. During the postoperative period rapid hematogenous spread of tuberculosis developed with progressive reduction of respiratory function followed by ARDS. Autopsy revealed tuberculosis in all organs including the transplanted kidney.

Relationship between generation and plasma concentration of anorganic phosphorus. In vivo studies on dialysis patients and in vitro studies on erythrocytes.

The plasma concentration of inorganic phosphorus (Pi) was determined before, during and after hemodialysis in 28 patients with chronic renal failure. Pi plasma concentration decreased rapidly when hemodialysis was started but did not fall below normal levels during continued dialysis. These changes of Pi concentration were fitted to a model of Pi kinetics in which Pi delivery to plasma is a nonlinear function of the extracellular Pi concentration. In separate in vitro studies, erythrocytes from six subjects with normal renal function and from 14 patients with chronic renal failure were incubated in homologous plasma with various amounts of Pi added. All other factors known to affect the Pi shift between intra- and extracellular fluid compartments (pH, calcium concentration) were kept constant. The relation between Pi concentration in plasma used for incubation and in red cells after 1h incubation suggested a mechanism in which a high plasma concentration results in movement of Pi into red cells where Pi is stored most probably in glucose esters. At low Pi plasma concentration Pi is delivered to plasma at a rate which cannot be explained solely by passive movement of intracellular Pi to plasma but requires additional generation from intracellular storage forms. The generation and delivery of Pi in patients and in their erythrocytes indicate a simple cell-mediated Pi homeostasis counter-acting abnormal fluctuations of plasma Pi.