[Proteinuria: pathophysiology and clinical implications]. / Protéinurie: rappel physiologique et applications pratiques.

Pathological proteinuria is a sign of renal disease, either tubular or glomerular. Proteinuria is considered as a major renal and cardiovascular risk factor Screening, and quantification of proteinuria is part of the care of chronic kidney disease (CKD) patients, but also of high renal risk patients and high cardiovascular risk patients. CKD is now classified according to estimated GFR and proteinuria to improve prediction of adverse events. in this article, we summarize the pathophysiology of proteinuria, its clinical qualification and implications.

[Diabetic nephropathy: an update]. / Néphropathie diabétique.

Diabetes has a constantly growing prevalence and leads to a number of complications such as diabetic nephropathy. A systematic screening and an adapted management are needed to limit the renal and also the cardiovascular complications linked to diabetic nephropathy. An adequate glycemic and tensional control and control of proteinuria are the priority in the care of diabetic nephropathy. Other aspects such as phospho-calcium balance, lipid panel or lifestyle changes are also important and therefore a multidisciplinary approach is essential. A better understanding of the physiopathology may lead to even more effective treatments in the future. We resume in this article the actual management of a patient suffering from diabetic nephropathy and the future treatment perspectives.

Management of patients with nephrotic syndrome.

Nephrotic syndrome is characterised by proteinuria >3.5 g/24h, oedema, hypoalbuminaemia and hyperlipidaemia. Several glomerular diseases, either primary or secondary, may lead to nephrotic syndrome. Investigations for nephrotic syndrome include immunological and infectious evaluations. Renal biopsy is often mandatory, except in diabetes. Depending on aetiology specific treatment, often with immunosuppressive agents, may be implemented. In any cases nonspecific treatment should be started with ACE inhibitors or ARBs. Urinary protein loss leads to several complications: water and sodium retention, hyperlipidaemia, increased risk of thromboembolism and infection, anaemia and alteration of mineral metabolism. Each of these complications must be identified.

[Medical care of renal transplant recipients after the first year post-transplantation]. / Prise en charge médicale des patients greffés rénaux au-delà de la première année post-transplantation.

Kidney transplant recipients are a growing population in ambulatory care. Medical follow up after the first post transplant year requires a tight collaboration between transplant centers, primary care physicians and community nephrologists. Although kidney transplantation is the treatment of choice for patients in end stage renal failure, no major improvement has been seen in long-term patient and graft survivals. Mortality of kidney transplant recipients remains higher than that of the general population, due to the high incidence of cardiovascular disease, infection and malignancies related to progressive renal failure and also to immunosuppressive treatment. We review here the optimal ambulatory medical care needed by these patients after the first post transplant year.

New Magnetic Resonance Imaging Index for Renal Fibrosis Assessment: A Comparison between Diffusion-Weighted Imaging and T1 Mapping with Histological Validation.

A need exists to noninvasively assess renal interstitial fibrosis, a common process to all kidney diseases and predictive of renal prognosis. In this translational study, Magnetic Resonance Imaging (MRI) T1 mapping and a new segmented Diffusion-Weighted Imaging (DWI) technique, for Apparent Diffusion Coefficient (ADC), were first compared to renal fibrosis in two well-controlled animal models to assess detection limits. Validation against biopsy was then performed in 33 kidney allograft recipients (KARs). Predictive MRI indices, ΔT1 and ΔADC (defined as the cortico-medullary differences), were compared to histology. In rats, both T1 and ADC correlated well with fibrosis and inflammation showing a difference between normal and diseased kidneys. In KARs, MRI indices were not sensitive to interstitial inflammation. By contrast, ΔADC outperformed ΔT1 with a stronger negative correlation to fibrosis (R(2) = 0.64 against R(2) = 0.29 p < 0.001). ΔADC tends to negative values in KARs harboring cortical fibrosis of more than 40%. Using a discriminant analysis method, the ΔADC, as a marker to detect such level of fibrosis or higher, led to a specificity and sensitivity of 100% and 71%, respectively. This new index has potential for noninvasive assessment of fibrosis in the clinical setting.

Acute and long term mineral metabolism adaptation in living kidney donors: a prospective study.

BACKGROUND: Living kidney donors (LKDs) experience an abrupt decline in glomerular filtration rate (GFR). Mineral metabolism adaptations in early CKD are still debated and not well studied in LKDs. We prospectively studied acute and long term mineral metabolism adaptation of LKDs. METHODS: From May 2010 to December 2012, we included 27 adult LKDs. Their mineral parameters and renal function were repeatedly measured at days 0, 1, 2, 3, 180 and 360 after donation. We also measured in uninephrectomized rats' Klotho in the remnant kidney and FGF23 circulating levels. RESULTS: In the first days after nephrectomy, LKDs experience transient dilution hypocalcemia and secondary hyperparathyroidism. Urinary phosphate reabsorption decreases in spite of an abrupt decline in circulating FGF23 and Klotho. In a more chronic stage, at days 180 and 360 after donation, LKDs have lower GFR and 1,25(OH)2D compared to pre-donation levels, with unchanged 25(OH)D. PTH levels increase, resulting in decreased plasma phosphate levels and renal tubular reabsorption of phosphate. In comparison to pre-donation, FGF23 levels are not significantly changed whereas circulating Klotho levels are lower than pre-donation but higher than immediately post-donation. In uninephrectomized rats, Klotho kidney expression increases after three weeks, whereas circulating FGF23 levels are unchanged. CONCLUSION: From six months after kidney donation, LKDs develop secondary hyperparathyroidism related to a decrease in 1,25(OH)2D, and decreased plasma phosphate levels. FGF23 levels do not rise in LKDs. Middle term mineral metabolism adaptations to decreased eGFR in donors include decrease in 1,25(OH)2D and increase in PTH and fractional excretion of phosphate resulting in lowered plasma phosphate levels, independently of FGF23. These adaptations differ from those described in CKD patients.

Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure.

Acute renal failure (ARF) in critically ill patients is associated with high mortality. Optimal method and dose of continuous renal replacement therapy could improve survival in these patients. We studied the hypothesis that an increase in dialysis dose obtained by continuous veno-venous hemodiafiltration (CVVHDF) is associated with a better survival than continuous veno-venous hemofiltration (CVVH) among critically ill patients with ARF. In a prospective randomized trial, these two methods were compared in patients undergoing renal replacement therapy in two intensive care units (ICUs). The patients had either CVVH (1-2.5 l/h replacement fluid) or continuous CVVHDF (1-2.5 l/h replacement fluid+1-1.5 l/h dialysate) according to their body weight. 28- and 90-day mortalities, renal recovery, and duration of ICU stay were the main outcome measures. Two hundred and six patients were randomized from October 2000 to December 2003. Twenty-eight-day survivals (%) were, respectively, 39 and 59 (P=0.03) in the CVVH and CVVHDF groups. Three months survivals (%) were, respectively, 34 and 59 (P=0.0005) in the CVVH and CVVHDF groups. Apache II score, age, baseline blood urea nitrogen, and hemodiafiltration (hazard ratio 0.59, 95% confidence interval 0.40-0.87; P=0.008) were independent predictors of survival at 90 days. Renal recovery rate among survivors (71 versus 78% in the CVVH and CVVHDF groups respectively, P=0.62) was not affected by the type of renal replacement therapy. These results suggest that increasing the dialysis dose especially for low molecular weight solutes confers a better survival in severely ill patients with ARF.