Contributions to nephrology
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Stroke is a leading cause of mortality and morbidity worldwide. Traditional cardiovascular risk factors - hypertension, diabetes and dyslipidemia - are related to the incidence of stroke. Chronic kidney disease has also been recognized to be a major public health problem as a cardiovascular risk factor. ⋯ Chronic kidney disease may also be associated with an increase in nontraditional risk factors such as hyperhomocysteinemia, inflammation, asymmetric dimethylarginine, oxidative stress, and anemia, and thrombogenic factors such as left ventricular hypertrophy, endothelial dysfunction, and arterial stiffness. Herein, we review the results of meta-analyses of published cohort studies for a better understanding of the precise nature of the relationship between chronic kidney disease and stroke, important to both the clinical and public health fields. Further studies are warranted to determine whether interventions to prevent the progression of kidney impairment are effective at reducing the risk of stroke.
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Various drugs have been used for the treatment of focal segmental glomerular sclerosis (FSGS) or minimal change disease (idiopathic nephrotic syndrome, INS) including methylprednisolone pulses, alkylating agents and calcineurin inhibitors, often without a strong rationale. For some drugs the rationale has been recently provided by the identification of mechanisms regulating proteinuria. The characterization of molecules acting as permeability factors, including hemopexin, soluble urokinase receptor and cardiotrophin-like cytokine-1, supports plasma exchange in severe cases of INS, particularly in patients at high risk of recurrence of FSGS after transplantation. ⋯ Using saquinavir associated with small doses of calcineurin inhibitors, we treated a small series of very difficult cases of INS with insufficient response to steroid therapy and multiple immunosuppressive drugs. Saquinavir allowed a significant reduction of steroid cumulative doses and disappearance of features of steroid toxicity. In conclusion, recent reports have allowed a new insight into the pathogenetical mechanism regulating proteinuria in INS, offering new targets for treating severe cases.
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Pathophysiological mechanisms of cardiorenal syndromes (CRS) types 1-5 are still sparsely characterized. In an attempt to address this issue, a consensus conference on CRS was held in Venice, Italy, in November 2012 under the auspices of the Acute Dialysis Quality Initiative (ADQI). ⋯ Pre-conference we performed a systematic search and review of the available literature using a modified Delphi analysis. Hereby identified and in this review discussed questions were: (i) What are the predominant pathophysiologic mechanisms of CRS type 1 in acute decompensated heart failure? (ii) Could biomarker profiling identify pathomechanisms or hemodynamic phenotype of patients with CRS type 1? Could predictive biomarkers improve renal safety of therapy in CRS type 1? (iii) How do the timing, severity and duration relate to the mechanisms and outcomes of CRS type 1? In summary, after discussion and appraisal of the best available evidence, working group 1 makes consensus recommendations for future research on pathologic mechanisms of CRS type 1 and recommendations for clinical practice where treatment is in either proof or disproof of a mechanism.
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Chronic kidney disease and atrial fibrillation (AF) commonly coexist, and data suggest that renal patients have AF rates in excess of double that encountered in the general population. These patients are at increased risk of stroke, regardless of the presence or absence of AF. Furthermore, a lower GFR causes increased thromboembolic risk in patients with AF - independent of other risk factors. ⋯ The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion. There is a need for large randomised control trials in patients with renal insufficiency and on haemodialysis to provide a bank of high-quality scientific data on which clinicians can base their management decisions. Until then, we must adopt a pragmatic approach which involves careful consideration of the relative risk of stroke and bleeding in each individual patient.
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The parathyroid gland plays a central role in the regulation of mineral metabolism. In patients with chronic kidney disease (CKD), circulating levels of parathyroid hormone (PTH) are progressively increased as kidney function declines, as a result of phosphate retention, hypocalcemia, decreased production of 1,25-dihydroxyvitamin D [1,25(OH)2D], endogenous changes within the parathyroid gland, and skeletal resistance to the actions of PTH. In addition, the identification of fibroblast growth factor 23 (FGF23) and its cofactor Klotho offers important implications for the deeper understanding of disordered mineral metabolism in CKD. ⋯ FGF23 also acts directly on the parathyroid to decrease PTH synthesis and secretion, but this effect is blunted in advanced stages of CKD, due to decreased expression of the Klotho-FGF receptor 1 complex and increased concentrations of C-terminal FGF23 that competes with full-length FGF23 for binding to the receptor complex. Recent clinical studies also reported that high levels of FGF23 are associated with morbidity and mortality as well as treatment resistance to active vitamin D, suggesting the potential of FGF23 as a novel biomarker to guide treatment of disordered phosphate metabolism in CKD. This review will discuss the pathogenesis of secondary hyperparathyroidism, particularly focusing on the emerging role of the FGF23-Klotho axis in patients with CKD.