Loop diuretics improve conditions of dialysis inception in advanced CKD: an observational cohort study.

BACKGROUND: Diuretics can reduce fluid overload but their effects on conditions of dialysis start remain elusive. We aimed to determine whether loop diuretics exposure in the year before inception can delay the need for dialysis, affect the conditions of dialysis start, and cause early mortality three months after initiation in pre-dialysis patients. METHODS: All adult patients starting dialysis from 2009 to 2015 in the REIN registry were included. Three subgroups were defined according to diuretics exposure: "continuous", "stopped", or "no diuretics" over the year before inception and compared for pre-dialysis hospitalization rates, and 3-month mortality after dialysis. RESULTS: Among 59,302 patients, we found fewer emergency initiations of dialysis in the continuous diuretics group than in the stopped diuretics and no diuretics groups: 9492 (27.5%) vs 1905 (32.3%) and 5226 (35.0%), respectively; p < 0.0001. In the continuous diuretics group, there were fewer starts on central venous catheters than in the stopped diuretics and no diuretics groups: 16,677 (49.4%) vs. 3246 (56.0%) vs. 8,639 (58.4%); p < 0.0001. Patients with continuous diuretic exposure had a lower hospitalization rate than the stopped diuretics group in the year prior to dialysis, except for heart failure. The unadjusted 3-month hazard ratio of mortality after dialysis inception was significantly higher in the "no diuretics" or "stopped diuretics" groups compared with "continuous diuretics", but the excess of risk was blunted after adjustment for emergency start and pre-dialysis visits to a nephrologist. CONCLUSION: Continuous loop diuretics exposure in the year before dialysis was associated with better conditions of dialysis inception, and possibly lower mortality rates in the three months after inception.

Effects of high- vs low-dose native vitamin D on albuminuria and the renin-angiotensin-aldosterone system: a randomized pilot study.

BACKGROUND: Residual albuminuria is associated with an increased risk of progression to ESKD. We tested whether a supplementation with native vitamin D could reduce albuminuria in stable CKD patients under maximal renin-angiotensin system (RAS) blockade. METHODS: We conducted a randomized controlled study of high (cholecalciferol 100 000 UI per 10 days over 1 month) vs low-dose (ergocalciferol 400 UI/days over 1 month) supplementation with native vitamin D on urinary albumin/creatinine ratio, blood pressure and the RAS over 1 month in stable CKD patients with albuminuria and maximum tolerated RAS blockade. RESULTS: We included 31 patients, 21 in the high dose group and 10 in the low dose group. In contrast with a low dose, high dose vitamin D normalized plasma 25(OH)D, decreased iPTH but slightly increased plasma phosphate. High dose vitamin D decreased geometric mean UACR from 99.8 mg/mmol (CI 95% 60.4-165.1) to 84.7 mg/mmol (CI 95% 51.7-138.8, p = 0.046). In the low dose group, the change in geometric mean UACR was not significant. Blood pressure, urinary 24 h aldosterone and peaks and AUC of active renin concentrations after acute stimulation by a single dose of 100 mg captopril were unaffected by the supplementation in native vitamin D, irrespective of the dose. Native vitamin D supplementation was well tolerated. CONCLUSIONS: We found a small (- 15%) but significant decrease in albuminuria after high dose vitamin D supplementation. We found no effect of vitamin D repletion on blood pressure and the systemic RAS, concordant with recent clinical studies.

New-onset systemic sclerosis and scleroderma renal crisis under docetaxel.

Systemic sclerosis is a rare systemic autoimmune disease characterized by microvascular impairment and fibrosis of the skin and other organs with poor outcomes. Toxic causes may be involved. We reported the case of a 59-year-old woman who developed an acute systemic sclerosis after two doses of adjuvant chemotherapy by docetaxel and cyclophosphamide for a localized hormone receptor + human epithelial receptor 2-breast cancer. Docetaxel is a major chemotherapy drug used in the treatment of breast, lung, and prostate cancers, among others. Scleroderma-like skin-induced changes (morphea) have been already described for taxanes. Here, we report for the first time a case of severe lung and kidney flare with thrombotic microangiopathy after steroids for acute interstitial lung disease probably induced by anti-RNA polymerase III + systemic sclerosis after docetaxel.

Haemodialysis in patients treated with oral anticoagulant: should we heparinize?

BACKGROUND: Anticoagulation for the haemodialysis circuit in patients treated with oral anticoagulation poses additional haemorrhagic risk. The few available data suggest that tapering or even stopping heparinization is feasible and the HeprAN membrane with grafted heparin was developed to decrease heparin dose. The objective of our study was to evaluate the need for additional anticoagulation in patients on long-term oral anticoagulation, according to the type of membrane used. METHODS: This is a prospective, randomized, crossover bifactorial trial in haemodialysed patients on oral anticoagulation. Each patient had four haemodialysis sessions with two different membranes [HeprAN or polysulphone (PS)] and with or without enoxaparin. Clinical coagulation was evaluated by the need for premature ending and by a visual score (Janssen scale). Coagulation activation markers were also measured: d-dimers, prothrombin fragments 1 + 2, thrombin-antithrombin complexes, tissue factor pathway inhibitor and platelet factor-4. RESULTS: Ten patients were included (M/F = 4/6, mean age 63 ± 15 years). None of the 40 sessions ended prematurely. The clotting scores were similar with or without enoxaparin (dialyser: 1.49 ± 0.19 versus 1.53 ± 0.17, P = 0.97; bubble trap: 0.75 ± 0.19 versus 0.78 ± 0.22, P = 0.62) and with the polysulphone or the HeprAN membrane (dialyser: 1.54 ± 0.20 versus 1.47 ± 0.16, P = 0.65; bubble trap: 0.74 ± 0.22 versus 0.79 ± 0.19, P = 0.58). There was no significant difference in coagulation activation markers between dialysis modalities; however, dialysis efficacy was significantly greater with the PS membrane (1.58 ± 0.07 versus 1.43 ± 0.06, P = 0.02). CONCLUSIONS: These results suggest that haemodialysis without additional anticoagulation is possible in patients with oral anticoagulation. The HeprAN membrane did not provide any additional benefit compared with a PS membrane.

[Hypertensive nephrosclerosis]. / Néphroangiosclérose.

Hypertensive nephrosclerosis is the leading cause of end stage renal disease (ESRD) in France, however, in prospective clinical trials of hypertension, ESRD accounts only for a small fraction of all events (incidence rate 0.2 to 0.4% by year). Hypertensive nephrosclerosis is characterized histologically by a series of vascular injury, none of which is truly specific and that can be observed also in obesity or normal aging. Hypertensive nephrosclerosis is mildly symptomatic, but the prognosis is never benign, due to cardiovascular and renal burden. This unspecific presentation may explain why the diagnosis of hypertensive nephrosclerosis is easily carried by excess, the main differential diagnoses are atherosclerotic ischemic renal disease, poorly symptomatic primitive nephropathies or the sequelae of unnoticed malignant hypertensive nephrosclerosis. The very high prevalence of hypertensive nephrosclerosis in populations from African ancestry has suggested a genetic predisposition. MYH9/APOL1 gene variants have recently been identified and are strongly associated with hypertensive nephrosclerosis, however the pathophysiological link between these variants and renal disease is still unclear. The treatment is mainly based on blocking the renin angiotensin system, especially when proteinuria is present. The target blood pressure is less firmly established, the latest data from the AASK study, however, do suggest a benefit on progression of lower values < 135/80 or even < 130/80 mmHg, especially in patients with proteinuria.

[Nephroprotection, fact or fiction?]. / Les promesses de la néphroprotection à l'épreuve des faits.

Clinical studies of the last 15 years have shown the benefit of pharmacological interventions on the progression of chronic kidney disease, confirming the concept of nephroprotection. Pharmacological blockade of the renin angiotensin system remains the cornerstone of the nephroprotective treatment but the benefits and limitations are now better defined. The RAS blockers are all the more efficient than the proteinuria is abundant and nephroprotection is obtained in proportion to the reduction in proteinuria. Combinations of ACEI+ARA are not validated and their use should be considered only under the supervision of a specialist when optimal monotherapy has failed. The target blood pressure has been the subject of recent controversies, particularly in type 2 diabetic patients with nephropathy. The target should be individualized based on the main risk, renal or cardiovascular. Recent maneuvers have also shown a nephroprotective effect, including the correction of metabolic acidosis with sodium bicarbonate.

[Contrast-induced nephropathy]. / Insuffisance rénale aiguë liée aux produits de contraste iodés.

Acute kidney injury is a common complication after contrast administration in radiology or cardiology. It increases morbidity and in-hospital but also long-term mortality. The pathophysiology is complex, there is an association of direct cellular toxicity of contrast agents and medullary ischemia secondary to alterations in intra-renal hemodynamics and to an increase in metabolic activity. Many risk factors have been identified and should be checked prior to injection, the most important being pre-existing renal failure which might be identified by calculating the estimated glomerular filtration rate with predictive equations such as Cockcroft-Gault or MDRD equations. When risk factors are present and contrast administration is really necessary, the only validated measure to reduce the risk of renal failure is still volume expansion. Other pharmacological interventions have interesting results, but a confirmation on a larger scale is necessary. The volume expansion is best performed intravenously by the isotonic saline or sodium bicarbonate.

[Pathophysiology of kidney disease progression]. / Physiopathologie de la progression des maladies rénales.

Nephron reduction increases the filtration capacity of the remaining nephrons, which is helpful in the short term, but harmful over the long term The increase in glomerular capillary pressure and in hypertrophy of healthy nephrons stimulates the renin-angiotensin system and TGF-beta. Myofibroblastic transdifferentiation follows, with fibrogenesis and glomerulosclerosis. Converting enzyme inhibitors reduce the expression of genes coding for profibrotic molecules. Proteinuria promotes interstitial fibrosis and must be reduced by drugs that block the renin-angiotensin system.