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Background Renal function is known to affect glucose metabolism. The aim of this study was to assess glucose metabolism in end-stage renal disease (ESRD) patients and in matched controls with normal renal function and to delineate its underlying pathophysiology. Methods ESRD patients without diabetes mellitus on the active kidney transplant waiting list of a large European university hospital were metabolically phenotyped by an oral glucose tolerance test (OGTT) and by calculating insulin sensitivity and secretion indices. Matched controls with normal renal function were derived from the TUEF (Tuebingen Family) study cohort, which includes healthy non-diabetic individuals with an increased risk of developing type 2 diabetes. Matches were made for (i) gender, age and body mass index (BMI) (cohort 1) and for (ii) gender, age, BMI, fasting plasma glucose (FPG) and 2-h glucose in OGTT (cohort 2). Results A total of 107 patients (90 on haemodialysis and 17 on peritoneal dialysis) and two cohorts, each comprising 107 matched controls, were investigated. ESRD patients had significantly lower FPG. Additional matching for OGTT glucose concentrations revealed significantly lower insulin sensitivity in ESRD patients than in controls. This finding was abrogated after adjustment for triglyceride levels. Insulin secretion, however, was significantly higher in ESRD patients. Insulin kinetics during OGTT as well as C-peptide levels demonstrate higher insulin secretion to be a compensation for lower insulin sensitivity and not to result from impaired insulin clearance. Conclusion Our study is the first to provide metabolic phenotyping in patients with ESRD and to compare them with matched controls with normal renal function. Glucose metabolism differs substantially between cohorts, with insulin resistance and a compensatory increase in insulin secretion in ESRD patients.

Die diabetische Nephropathie ist in der entwickelten Welt die häufigste Ursache eines dialysepflichtigen Nierenversagens. Eine erhöhte Albuminausscheidung im Urin ist charakteristisch für eine diabetische Nierenschädigung. Regelmässiges Mikroalbuminurie-Screening ermöglicht Früherkennung und frühzeitige Intervention. Bei manifester diabetischer Nephropathie dient eine Quantifizierung der Albuminurie der Verlaufsbeobachtung. Therapeutische Interventionen, die die Albuminurie zu reduzieren vermögen, verlangsamen die Progression einer diabetischen Nierenschädigung und reduzieren überdies die kardiovaskuläre Mortalität, da die Albuminurie einen unabhängigen kardiovaskulären Risikofaktor darstellt. Diese Übersichtsarbeit beschreibt den klassischen Verlauf der diabetischen Nephropathie und bespricht praxisrelevante Aspekte bei der Bestimmung der Albuminurie. Verfügbare prophylaktische und therapeutische Interventionen, allen voran Blutzuckerkontrolle und Hemmung des Renin-Angiotensin-Aldosteron-Systems, werden in einer evidenzbasierten Weise diskutiert.

Das terminale Nierenversagen mit der Nierenfibrose als pathologischem Korrelat zwingt in Deutschland jährlich zahlreiche Menschen zu einer lebenseinschränkenden Therapie und geht einher mit einer erhöhten Mortalität. In der vorliegenden Arbeit konnte anhand einer in vivo-Studie gezeigt werden, dass Kalzium-abhängige Kaliumkanäle, im Speziellen KCa3.1, die Krankheitsprogression beeinflussen. Eine pharmakologische Blockade des Kanals könnte ein wichtiger Ansatzpunkt für die Zukunft sein., End stage renal disease, in particular renal fibrosis as pathological result, forces patients into a hard therapy and increases mortality rate. The following in vivo studies are about calcium-activated potassium channels, in particular KCa3.1, and their crucial importance in progressing renal fibrosis. A pharmacological blockade of the channel could be an important starting point for the future.

Health political background In 2006, the prevalence of chronic renal insufficiency in Germany was 91,718, of which 66,508 patients were on dialysis. The tendency is clearly growing. Scientific background Chronic renal insufficiency results in a disturbance of the mineral balance. It leads to hyperphosphataemia, which is the strongest independent risk factor for mortality in renal patients. Usually, a reduction in the phosphate intake through nutrition and the amount of phosphate filtered out during dialysis are not sufficient to reduce the serum phosphate values to the recommended value. Therefore, phosphate binders are used to bind ingested phosphate in the digestive tract in order to lower the phosphate concentration in the serum. Four different groups of phosphate binders are available: calcium- and aluminium salts are the traditional therapies. Sevelamer and Lanthanum are recent developments on the market. In varying doses, all phosphate binders are able to effectively lower phosphate concentrations. However, drug therapies have achieved recommended phosphate levels in only 50 percent of patients during the last years. Research questions How effective and efficient are the different phosphate binders in chronic renal insufficient patients? Methods The systematic literature search yielded 1,251 abstracts. Following a two-part selection process with predefined criteria 18 publications were included in the assessment. Results All studies evaluated conclude that serum phosphate, serum calcium and intact parathyroid hormone can be controlled effectively with all phosphate binders. Only the number of episodes of hypercalcaemia is higher when using calcium-containing phosphatebinders compared to Sevelamer and Lanthanum. Regarding the mortality rate, the cardiovascular artery calcification and bone metabolism no definite conclusions can be drawn. In any case, the amount of calcification at study start seems to be crucial for the further development of the cardiovascular calcification. Economic studies show higher costs for Sevelamer and Lanthanum compared to calcium-containing phosphate binders. Discussion Only a few well documented primary studies on the effectiveness of phosphate binders are available. Particularly long-term studies with a robust study design and transparent documentation are lacking. Ten of the eleven primary studies included in this report were conducted in only 539 patients from five patient collectives. Conclusions From a medical point of view, Sevelamer shows some superiority over calcium-containing phosphate binders based on the current data, at least for special indications. The validity of the present Health Technology Assessment (HTA) report is significantly limited due to the limited number of available publications, the low sample size of treated patients, as well as the fact that the majority of studies are based on the same patient collectives. Prospective long-term studies not funded by the industry with adequate sample sizes and comparable study designs are called for to make authoritative statements regarding the medical effectiveness and safety of Sevelamer and Lanthanum, as well as regarding their economic efficiency., GMS Health Technology Assessment; 5:Doc08; ISSN 1861-8863

Nephrocalcinosis is the result of a myriad of hereditary or acquired diseases in the calcium, phosphate or oxalate metabolism that lead to deposition of calcium containing precipitates within the kidney. Nephrocalcinosis and nephrolithiasis are pathophysiologically tightly related and often co-exist. In the case of recurrent nephrolithiasis, nephrocalcinosis has to be excluded. Stone analysis can yield important clues to the underlying disease process. The best way to diagnose nephrocalcinosis and an accompanying nephrolithiasis is by native computer tomography scans. Untreated, nephrocalcinosis will lead to a progressive decline in renal function and eventually to end stage renal disease. Thus, for each case, the underlying disease process has to be determined and a causative therapy initiated.

The pathogenesis of terminal renal failure is discussed. The following are distinguished: 1. Renal failure occurring against a background of decompensated benign nephrosclerosis, primary and secondary malignant nephrosclerosis, and stenosis of the renal artery. 2. Renal failure caused by loss of glomeruli. It is pointed out that in most glomerulopathies, including diabetic glomerulopathy and renal amyloidosis, terminal renal failure only develops when accompanying disease of the postglomerular vessels leading to interstitial fibrosis impairs the outflow of blood from the glomerulus to such an extent that no more urine is produced. 3. Renal failure in disease of the tubules themselves. It is emphasized that acute renal failure only becomes chronic when interstitial fibrosis develops from the interstitial edema occurring in the early stage of the disease. 4. Renal failure occurring in primary diseases of the renal cortical interstitium. The chronic sclerosing renal diseases arising from acute interstitial nephritis are dealt with, as also are reflux nephropathy, incomplete obstructive nephropathy, analgesic nephropathy, and chronic interstitial rejection reactions in transplanted kidneys.