Silent chronic kidney disease epidemic seen from Europe: designing strategies for clinical management of the early stages.

Given the alarming predictions of the potentially devastating future epidemic of end-stage renal disease (ESRD), further knowledge is still urgently needed on this topic. The real dimensions of the problem are still unclear. It is difficult to compare Europe and the USA because different criteria are used in data collection and not much information is available, but the epidemic of silent chronic kidney disease seems to be more widespread in the States than in Europe, and more severe in terms of cardiovascular mortality. Defining early chronic renal insufficiency carrying a definite risk of ESRD is not easy, particularly for chronic renal conditions in which the clinical picture is still faint and the renal dysfunction minimal. It is also hard to say which tools are most suitable for diagnosing such renal disorders (renal filtration indexes vs. composite indexes of renal damage, e.g. the NKF's CKD stages). Furthermore, it is still not clear which strategies best identify subjects with these conditions (screening vs. early interception; general population vs. high-risk groups), how effective therapeutic approaches are, which subject categories benefit from early diagnosis and intervention, and how clinical measures should be structured (multidisciplinary case management-based approaches vs. general practitioner-oriented approaches). These issues are discussed in this paper.

Management of hypertension in chronic kidney disease: the Italian multicentric study.

BACKGROUND: Guidelines have indicated the achievement of blood pressure target (BP <130/80 mmHg) as a priority in the conservative treatment of chronic kidney disease (CKD), but the current implementation of these recommendations in clinical practice is unknown. METHODS: We assessed control rates, treatment and clinical correlates of hypertension in 1201 adult non-dialyzed CKD patients followed up by a nephrologist for at least 6 months. RESULTS: Estimated glomerular filtration rate (GFR) was 32 (SD 15) mL/min/1.73 m2. BP target was not achieved in 88% of patients (95% confidence interval (95% CI): 86-90%). In 84% of patients, BP levels were also above the target at the first visit to the nephrology unit 4.5 yrs previously. The risk of not achieving BP target during the nephro-logy follow-up was associated with older age (odds ratio (OR): 1.24, 95% CI 1.06-1.45, p=0.008), diabetes (OR: 2.25, 95% CI 1.20-4.20, p=0.011), and the duration of hypertension (OR: 1.13, 95% CI 1.02-1.24, p=0.016). Among patients with uncontrolled BP, about 70% received multidrug antihypertensive therapy including renin-angiotensin system (RAS) inhibitors; conversely, diuretic treatment was prescribed in a minority of patients (37%), and at insufficient doses in half the cases, despite the insufficient implementation of a low salt diet (18%). CONCLUSIONS: BP target was not reached in most CKD patients routinely seen in the renal clinics. The main barrier to guideline implementation is possibly the inadequate treatment of extracellular volume expansion despite the large prevalence of factors, such as older age and diabetes, which further enhance the intrinsic BP salt sensitivity of CKD.

An unusual association of contralateral congenital small kidney, reduced renal function and hyperparathyroidism in sponge kidney patients: on the track of the molecular basis.

Of unknown pathogenesis, sponge kidney (SK) is variably associated with nephrocalcinosis, stones, nephronic tubule dysfunctions and precalyceal duct cysts. Amongst 72 unrelated renal SK patients with renal stone disease, we detected one with unilateral bifid renal pelvis and six with unilateral small kidneys (longitudinal diameter difference >15%). Secondary causes of small kidney were excluded. Of the seven cases, four had reduced renal function (67 vs 7% in the entire cohort), and three developed hyperparathyroidism during follow-up (43 vs 4%). The pathogenesis of SK ought to explain why anatomical structures of different embryological origin are involved (the precalyceal and collecting ducts and the nephron) and why there is frequent association with hyperparathyroidism. In embryogenesis, the metanephric blastema synthesizes the chemotactic glial-derived neurotrophic factor (GDNF) to prompt the ureteric bud to branch off from Wolff's mesonephric duct, and to approach and invade the blastema. The bud's tip expresses the GDNF receptor (RET). RET-GDNF binding is crucial not only for the correct formation of ureters and collecting ducts (both of Wolffian origin), but also for nephrogenesis. We advance the hypothesis that SK results from a disruption in the ureteric bud-metanephric blastema interface, possibly due to one or more mutations or polymorphisms of RET or GDNF genes. This would explain: the concurrent alterations in precalyceal ducts and the functional defects in the nephron, the occasional association with size and the functional asymmetry between the two kidneys, some degree of renal dysplasia causing the reduction in the glomerular filtration rate and (given the role of RET in parathyroid cell proliferation) the association with hyperparathyroidism.