[Dialysis: past, present, future. Between technology and ecology]. / Dialyse : passé, présent, futur. Entre technologie et écologie.

Dialysis, hemodialysis or peritoneal dialysis, allows the purification of body waste, the elimination of excess water (ultrafiltration) and the restoration of homeostasis. The treatment is nevertheless cumbersome and burdened with multiple constraints that have changed little over the last 70 years. The ecological balance of hemodialysis is also very heavy. Advances, both ecological and technological, have been announced for the next few years, so we will take a look at them.

La dialyse, l'hémodialyse ou la dialyse péritonéale, permettent l'épuration des déchets de l'organisme, l'élimination de l'eau en excès (ultrafiltration) et le rétablissement de l'homéostasie. Le traitement est néanmoins lourd et grevé de multiples contraintes qui n'ont que peu évolué ces 70 dernières années. Le bilan écologique de l'hémodialyse est également très lourd. Des avancées écologiques et technologiques, dont nous faisons un tour d'horizon dans cet article, sont annoncées pour les prochaines années.

[When necrosis threatens the kidney patient ]. / Quand la nécrose guette l'insuffisant rénal .

Calciphylaxis is a rare but devastating condition characterized by a calcifying thrombosing microangiopathy resulting in painful necrotic skin lesions. Risk factors are multiple, the most important being obesity, disorders of phosphocalcic metabolism and acenocoumarol. Largely unknown by the medical community, its pathogenesis is still incompletely elucidated; its diagnosis by skin biopsy remains difficult and increasingly debated because potentially associated with an aggravation of lesions. Its treatment must be as premature as possible andmultimodal. However, the results are up to now unsatisfactory, as specific treatment of calciphylaxis does not yet exist.

La calciphylaxie est une pathologie rare mais dévastatrice qui survient surtout chez les patients souffrant d'une maladie rénale terminale. Elle est caractérisée par une microangiopathie calcifiante et thrombosante qui engendre des lésions cutanées nécrotiques et douloureuses. Les facteurs de risque sont multiples : les plus importants sont l'obésité, les troubles du métabolisme phosphocalcique et les anticoagulants coumariniques. Encore peu connue du monde médical, sa pathogenèse est encore incomplètement élucidée ; le diagnostic par biopsie cutanée reste difficile et débattu, car potentiellement associée à une aggravation des lésions. La prise en charge doit être précoce et multimodale ; elle reste jusqu'à présent insatisfaisante, un traitement ciblé étant toujours inexistant.

[Clinical use of tolvaptan: a 2021 review]. / Histoire d'eau : le tolvaptan dans tous ses états.

Along with the arrival of the first vasopressin-receptor V2R inhibitor, the indications for its use have increased. We review here and focus on polycystic kidney disease (PKD) and hyponatremia. Tolvaptan is the first drug available to slow down the progression of PKD in patients with rapid progressing disease. However, the benefits are moderate and the side effects are important, making important to share the decision of treatment together with the patient. Hyponatremia with preserved extra-cellular volume or associated with edema may be reversed by tolvaptan. Patients with SIADH or hyponatremia and edema might benefit from this treatment under strict monitoring. Overall, vaptans are helpful in several conditions, but remain tools that must be used under close control.

Depuis l'arrivée des inhibiteurs des récepteurs rénaux à la vasopressine V2, les indications à leur utilisation ont explosé. Nous revoyons ici certaines d'entre elles, en particulier la polykystose rénale et l'hyponatrémie. Première molécule à ralentir la progression de la polykystose rénale, le tolvaptan est réservé à des patients très motivés, dont la maladie progresse rapidement. En effet, les bénéfices sont modérés et les effets secondaires importants. La décision de traiter doit donc être partagée avec le patient. L'hyponatrémie à volume conservé ou liée à des œdèmes peut être corrigée par le tolvaptan. Les patients avec syndrome de sécrétion inappropriée d'hormone antidiurétique ou avec œdèmes peuvent en bénéficier sous certaines conditions et sous stricte surveillance. Le tolvaptan permet d'améliorer plusieurs pathologies, mais exige une étroite surveillance.

[Acid uric : key player in a recently recognized devastating nephropathy and in the development of chronic kidney disease.] / Acide urique : coupable d'une mystérieuse néphropathie aiguë et complice de la maladie rénale chronique ?

Uric acid has been known since long ago for its implication in gout and in certain kinds of nephrolithiasis. However, its role in models of acute and chronic nephropathies has been the focus of many new developments. The so called Mesoamerican nephropathy is a devastating disease that has caused more than 20'000 deaths in central America these last few years among sugarcane workers. Acid uric could play a key role in its physiopathology. Moreover, acid uric tends to be recognized as an independent factor of development and progression in chronic kidney disease, opening a way for new therapeutic targets.

L'acide urique est bien connu comme agent pathogène de la goutte et de certains calculs rénaux. Son implication, aussi bien dans des modèles aigus que chroniques de maladies rénales, a été l'objet de plusieurs développements récents. La néphropathie mésoaméricaine est en effet responsable de plus de 20 000 décès ces dernières années, principalement chez des jeunes agriculteurs qui récoltent la canne à sucre. Il semble que la production massive d'acide urique lors d'épisodes répétés d'hypovolémie soit un facteur déterminant. Par ailleurs, des données tendent à démontrer que l'acide urique est un facteur de risque indépendant dans le développement et la progression de la maladie rénale chronique, ouvrant la voie à de potentielles implications thérapeutiques.

Risk factors for community-acquired acute kidney injury in patients with and without chronic kidney injury and impact of its initial management on prognosis: a prospective observational study.

BACKGROUND: We aimed to describe clinical characteristics of patients with community-acquired acute kidney injury (CA-AKI), the effectiveness of initial management of CA-AKI, its prognosis and the impact of medication on its occurrence in patients with previous chronic kidney injury (CKI). METHODS: We undertook a prospective observational study within the Emergency Department (ED) of a University Hospital, screening for any patient >16 years admitted with an eGFR <60 ml/mn/1.73 m2 and a rise in serum creatinine as compared to previous values. Patients' medical files were reviewed by a panel of nephrologists in the subsequent days and at one and three-years follow-up. RESULTS: From May 1st to June 21st 2013, there were 8464 admissions in the ED, of which 653 had an eGFR <60 ml/mn/1.73 m2. Of these, 352 had previous CKI, 341 had CA-AKI, and 104 had CA-ACKI (community-acquired acute on chronic kidney injury). Occurrence of superimposed CA-AKI in CKI patients was associated with male gender and with use of diuretics, but not with use of ARBs or ACEIs. Adequate management of CA-AKI defined as identification, diagnostic procedures and therapeutic intervention within 24 h, was recorded in 45% of the cases and was not associated with improved outcomes. Three-year mortality was 21 and 48% in CKI and CA-ACKI patients respectively, and 40% in patients with only CA-AKI (p < 0.001). Mortality was significantly associated with age, hypertension, ischemic heart disease and CA-AKI. Progression of renal insufficiency was associated with male gender and age. CONCLUSIONS: CA-AKI is more frequently encountered in male patients and those treated with diuretics and is an independent risk factor for long-term mortality. Its initial adequate management failed to improve outcomes.

Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease.

In rodents, parietal epithelial cells (PECs) migrating onto the glomerular tuft participate in the formation of focal segmental glomerulosclerosis (FSGS) lesions. We investigated whether immunohistologic detection of PEC markers in the initial biopsies of human patients with first manifestation of idiopathic nephrotic syndrome with no immune complexes can improve the sensitivity to detect sclerotic lesions compared with standard methods. Ninety-five renal biopsies were stained for claudin-1 (PEC marker), CD44 (activated PECs), and LKIV69 (PEC matrix); 38 had been diagnosed as early primary FSGS and 57 as minimal change disease. PEC markers were detected on the tuft in 87% of the biopsies of patients diagnosed as primary FSGS. PEC markers were detected in FSGS lesions from the earliest stages of disease. In minimal change disease, no PEC activation was observed by immunohistology. However, in 25% of biopsies originally diagnosed as minimal change disease the presence of small lesions indicative of a sclerosing process were detected, which were undetectable on standard periodic acid-Schiff staining, even though only a single histologic section for each PEC marker was evaluated. Staining for LKIV69 detected lesions with the highest sensitivity. Two novel PEC markers A-kinase anchor protein 12 and annexin A3 exhibited similar sensitivity. In summary, detection of PECs on the glomerular tuft by immunostaining improves the differentiation between minimal change disease and primary FSGS and may serve to guide clinical decision making.

Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial.

INTRODUCTION: A systemic anticoagulation is often required to prevent circuit and filter clotting in ICU patients undergoing continuous renal replacement therapy (CRRT). A regional citrate-based anticoagulation (RCA) does not induce a systemic anticoagulation and prolongs the filter lifespan, but metabolic side-effects have been associated with this therapy. We conducted a randomized controlled trial with patients requiring CRRT to determine whether RCA using a balanced predilution replacement fluid is more effective than heparin in terms of renal replacement delivered dose and safety profile. METHODS: One hundred and three patients with AKI requiring CRRT were included. The patients were randomized to either CRRT with RCA or heparin anticoagulation. Primary endpoints were effective daily delivered RRT dose during the first 3 days of CRRT and filter lifespan. Secondary endpoints were 28-day and 90-day survival and severe metabolic complications and bleeding disorders. RESULTS: Median CRRT duration was 3.0 (2-6) days. Effective delivered daily RRT doses were 29 ± 3 and 27 ± 5 mL/kg/hr in the RCA and heparin groups, respectively (p = 0.005). Filter lifespans were 49 ± 29 versus 28 ± 23 hrs in the RCA and heparin groups (p = 0.004). Survival rates at 28 and 90 days were 80-74% in the RCA and 74-73% in the heparin group. Electrolytes and acid-base disturbances were uncommon and transient in patients treated with RCA. CONCLUSIONS: These results show that RCA is superior to heparin-based anticoagulation in terms of delivered RRT dose and filter life span and is a safe and feasible method. This does not translate into an improvement in short term survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT01269112 . Registered 3rd January 2011.

Increased risk of solid renal tumors in lithium-treated patients.

Cystic kidney diseases and toxic interstitial nephritis may be complicated by renal tumors. Long-term lithium intake is associated with tubulointerstitial nephritis and renal cysts but to date such an association with tumors has not been determined. We evaluated this in a retrospective study to determine whether lithium-treated patients were at higher risk of renal tumors compared with lithium-free patients with chronic kidney disease (CKD), and to the general population. Over a 16-year period, 14 of 170 lithium-treated patients had renal tumors, including seven malignant and seven benign tumors. The mean duration of lithium exposure at diagnosis was 21.4 years. The renal cancers included three clear-cell and two papillary renal cell carcinomas, one hybrid tumor with chromophobe and oncocytoma characteristics, and one clear-cell carcinoma with leiomyomatous stroma. The benign tumors included four oncocytomas, one mixed epithelial and stromal tumor, and two angiomyolipomas. The percentage of renal tumors, particularly cancers and oncocytomas, was significantly higher in lithium-treated patients compared with 340 gender-, age-, and estimated glomerular filtration rate (eGFR)-matched lithium-free patients. Additionally, the Standardized Incidence Ratio of renal cancer was significantly higher in lithium-treated patients compared with the general population: 7.51 (95% confidence interval (CI) (1.51-21.95)) and 13.69 (95% CI (3.68-35.06)) in men and women, respectively. Thus, there is an increased risk of renal tumors in lithium-treated patients.

[Epidemiology of community-acquired acute kidney injury]. / Epidémiologie de l'insuffisance rénale aiguë acquise dans la communauté.

Community-acquired acute kidney injury (CA-AKI) is on the rise and is nowadays a major public health problem. In the western world, CA-AKI concerns in priority elderly patients with multiple comorbidities and treated with nephrotoxic medications. Earlier detection of patients at risk and teaching them how to prevent CA-AKI will minimize its prevalence and complications.

Comparative efficacy of patiromer and sodium polystyrene sulfonate on potassium levels in chronic haemodialysis patients: a randomized crossover trial.

Background: Hyperkalaemia is frequent in haemodialysis (HD) patients and associated with increased cardiovascular mortality. Despite routine clinical use, evidence regarding the efficacy of potassium (K+) binders in HD is scant. We wished to compare the efficacy of patiromer (PAT) and sodium polystyrene sulfonate (SPS) on K+ levels in this setting. Methods: We screened patients in three HD centres with pre-HD K+ value between 5.0 and 6.4 mmol/L, after an initial 2-week washout period for those previously on K+ binders. We included patients in an unblinded two-arm crossover trial comparing SPS 15 g before each meal on non-dialysis days with PAT 16.8 g once daily on non-dialysis days with randomized attribution order and a 2-week intermediate washout period. The primary outcome was the mean weekly K+ value. Results: We included 51 patients and analysed 48 with mean age of 66.4 ± 19.4 years, 72.9% men and 43.4% diabetics. Mean weekly K+ values were 5.00 ± 0.54 mmol/L, 4.55 ± 0.75 mmol/L and 5.17 ± 0.64 mmol/L under PAT (P = .003), SPS (P < .001) and washout, respectively. In direct comparison, K+ values and prevalence of hyperkalaemia were lower under SPS as compared with PAT (P < .001). While the incidence of gastrointestinal side effects was similar between treatments, SPS showed lower subjective tolerability score (6.0 ± 2.4 and 6.9 ± 1.9) and compliance (10.8 ± 20.4% and 2.4 ± 7.3% missed doses) as compared with PAT (P < .001 for both). Conclusion: Both PAT and SPS are effective in decreasing K+ levels in chronic HD patients. However, at the tested doses, SPS was significantly more effective in doing so as compared with PAT, despite lower tolerability and compliance. Larger randomized controlled trials should be conducted in order to confirm our findings and determine whether they would impact clinical outcomes.

[Immunosuppressive drugs - how they work, their side effects and interactions]. / Immunsuppressiva - Wirkungen, Nebenwirkungen und Interaktionen.

The central issue in organ transplantation remains suppression of allograft rejection. Immunosuppression can be achieved by depleting lymphocytes, diverting lymphocyte traffic, or blocking lymphocyte response pathways. Immunosuppressive drugs include small-molecule drugs, depleting and nondepleting protein drugs (polyclonal and monoclonal antibodies), fusion proteins, intravenous immune globulin, and glucocorticoids. Small-molecule immunosuppressive agents include calcineurin-inhibitors (cyclosporine, tacrolimus), Target-of-Rapamycin Inhibitors (Sirolimus, Everolimus), inhibitors of nucleotide synthesis and azathioprine. The review covers the mode of action of these drugs with a special focus on belatacept, a new promising fusion protein. Different immuo-suppressive strategies mean also different safety profiles. Common side effects include the consequences of diminished immuno- response, i.e. infections and cancer (mainly involving the skin). Toxic side effects of immunosuppressive drugs range in a wide spectrum that involves almost every organ. The major interest of this toxic effects is the cardiovascular tolerance (with large differences from drug to drug), that are discussed seperately. The calcineurin- and mTOR-inhibitors are both metabolized by the CYP450 3A4 enzyme, which is also involved in the metabolism of many other drugs. The review discusses the most important interactions that in- or decreases the through level of these drugs.

Procalcitonin and infection in elderly patients.

OBJECTIVES: To compare the usefulness of procalcitonin (PCT) in detecting infection in elderly patients with that of other clinical and biological markers. DESIGN: Prospective observational study to compare PCT levels in infected and uninfected patients. SETTING: Geriatric teaching hospital in Switzerland. PARTICIPANTS: Two hundred eighteen elderly patients aged 75 and older admitted to an acute geriatric care unit. MEASUREMENTS: Demographic characteristics, comorbidities, Charlson index, general signs (respiratory rate, temperature, pulse rate, confusion, falls, shivering), presence of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, functional score (Functional Independence Measurement (FIM)) biological parameters (PCT, C-reactive protein (CRP), leukocytes, albumin), and definite diagnosis at admission were collected prospectively for each patient. RESULTS: Long-term corticotherapy, chronic immune diseases, fever of 38 degrees C or higher, white blood cell count, pulse rate, FIM, SIRS, sepsis, CRP of 3 mg/mL or higher, and PCT of 0.5 ng/mL or higher were associated with an infection at admission. In multivariate analysis, only sepsis and CRP of 3 mg/mL or higher were still associated with an infection; PCT levels do not show any significant association in the multivariate analysis. In addition, when PCT had good specificity (94%), it had low sensitivity (24%). False-negative PCT was related to lower severity of infection (lower inflammatory reaction and lower acute renal failure) than true-positive PCT. This finding may also be related to aging per se. CONCLUSION: PCT may be useful to identify severely ill elderly patients admitted to an acute geriatric ward but not to discriminate patients with infection from those without.

Immunosuppressive drugs in organ transplant recipients--rationale for critical selection.

Transplantation is the treatment of choice for many different organ failures. Despite growing experience in surgery and immunosuppression protocols, the long-term mortality of the procedure remains much higher than in the general population. Second only to cardiovascular diseases as the cause of death in organ transplant recipients, cancer is now known to be at least partly related to the immunosuppression regimen. Nevertheless, if calcineurin inhibitors have a demonstrated pro-oncogenic effect, other classes, such as mTOR inhibitors, are antiproliferative, and even demonstrated as an efficient therapy in some advanced oncological situations. Therefore, the adaptation of the therapy protocol evolves now towards an individualized medicine based on the risk factors of each transplant recipient in terms of cardiovascular, infectious and oncological diseases. As the first organ involved by tumor is the skin, many different guidelines have been published to try and adapt the therapy to the occurrence of a new lesion. If, for example, limited actinic keratosis or the first episode of a non-melanoma skin cancer usually requires no change of the immunosuppressive therapy, but a local specialized care and frequent clinical controls, more advanced lesions imply the adaptation of the drug regimen. In any case, the collaboration between general practitioners, dermatologists and the transplantation team is mandatory.