Low exposition to lithium prevents nephrogenic diabetes insipidus but not microcystic dilations of the collecting ducts in long-term rat model.

Lithium induces nephrogenic diabetes insipidus (NDI) and microcystic chronic kidney disease (CKD). As previous clinical studies suggest that NDI is dose-dependent and CKD is time-dependent, we investigated the effect of low exposition to lithium in a long-term experimental rat model. Rats were fed with a normal diet (control group), with the addition of lithium (Li+ group), or with lithium and amiloride (Li+/Ami group) for 6 months, allowing obtaining low plasma lithium concentrations (0.25 ± 0.06 and 0.43 ± 0.16 mmol/L, respectively). Exposition to low concentrations of plasma lithium levels prevented NDI but not microcystic dilations of kidney tubules, which were identified as collecting ducts (CDs) on immunofluorescent staining. Both hypertrophy, characterized by an increase in the ratio of nuclei per tubular area, and microcystic dilations were observed. The ratio between principal cells and intercalated cells was higher in microcystic than in hypertrophied tubules. There was no correlation between AQP2 messenger RNA levels and cellular remodeling of the CD. Additional amiloride treatment in the Li+/Ami group did not allow consistent morphometric and cellular composition changes compared to the Li+ group. Low exposition to lithium prevented overt NDI but not microcystic dilations of the CD, with differential cellular composition in hypertrophied and microcystic CDs, suggesting different underlying cellular mechanisms.

[Nephroprotection: General principles and application to the patients with cancers - when nephroprotection is essential for oncological care plan]. / Néphroprotection : principes généraux et application au patient de cancérologie ­ quand la protection du rein est indispensable à la bonne conduite du plan de soin oncologique.

Nephroprotection is a set of recommendations that aim to prevent the risks of acute and/or chronic renal failure and to limit the progression of renal failure towards an end stage. Nephroprotection is not limited to nephrology and applies to all patients at risk of renal failure. Cancer patients are particularly at risk of developing intrinsic and extrinsic renal failure, as well as the toxicity of specific treatments. However, they are poorly included in nephroprotection studies. Thus, current guidelines have not been adapted to these pathologies and oncology-specific comorbidities, such as malnutrition or prognosis, are often not taken into account. In this article, we review the established recommendations by transposing them to the cancer patient as a whole. In addition to the reminder of hygiene and dietary rules to control blood pressure and diabetes, we discuss the importance of therapeutic education, iatrogeny and treatment options to control renal failure in this context. The lack of clearly established data in cancer confirms the needs to strengthen links between oncologists, hematologists and nephrologists and reinforces the emergence of onco-nephrology as a new discipline.

[Electrolyte disorders in oncological patients]. / Principaux troubles hydro-électrolytiques chez le patient de cancérologie.

Electrolyte disorders (ED) are common in patients with cancer and in most cases, the etiologies do not differ from the general population. They may also be induced by the cancer, its therapy or paraneoplastic syndromes. ED are associated with poor outcomes, increased morbidity and mortality in this population. Hyponatremia is the most common disorder, often multifactorial, iatrogenic or secondary to the syndrome of inappropriate antidiuretic hormone secretion, usually due to small cell lung cancer. More rarely, hyponatremia may reveal adrenal insufficiency. Hypokalemia is generally multifactorial and associated with other ED. Cisplatin and ifosfamide induce proximal tubulopathies with hypokalemia and/or hypophosphatemia. Hypomagnesemia is often iatrogenic, related to cisplatin or cetuximab, but can be prevented by supplementation. Hypercalcemia can impair life quality and be life-threatening in the most severe cases. Hypocalcemia is less common and often of iatrogenic origin. Finally, the tumor lysis syndrome is a diagnostic and therapeutic emergency that affects the prognosis of patients. Its incidence tends to increase in solid oncology, related to the improvement of therapies. Prevention and early diagnosis of ED are essential to optimize the overall management of patients with underlying cancer and cancer therapy. The aim of this review is to synthesize most frequent ED and their management.

[Renal failure in multiple myeloma: Specific management issues]. / Insuffisance rénale dans le myélome multiple : particularités de la prise en charge.

Renal impairment is common during multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Cast nephropathy, by monoclonal free light chains precipitation with uromodulin in renal tubules, is the main cause of acute kidney injury in multiple myeloma. Kidney biopsy, although not necessary for diagnosis, allows assessment of renal prognosis according to the extent of cast formation, tubular atrophy and interstitial fibrosis. Prevention and early diagnosis of acute kidney injury are essential to optimize management and avoid progression to chronic kidney disease. Rehydration, interruption of nephrotoxic treatments, correction of precipitating factors, anti-plasma cell chemotherapy can rapidly reduce the free light chains nephrotoxicity. The association of the proteasome inhibitor Bortezomib and high dose Dexamethasone is the reference treatment in newly diagnosed patients with renal impairment. Adding Cyclophosphamide or the immunomodulator Lenalidomide may improve the hematological response, but with a poorer tolerance. Use of anti-CD38 monoclonal antibodies is being evaluated in this population. Hemodialysis with high-flux or high-cut-off membranes, combined to chemotherapy, may improve renal function recovery. Management of multiple myeloma have to be adapted in patients with chronic kidney disease, dialysis or kidney transplantation. Because of improvement in global survival, kidney transplantation remains an option to consider in selected patients. Collaboration between hematologists and nephrologists is essential throughout the course of the disease.

Onco-nephrology: Physicians' Expectations About a New Subspecialty.

INTRODUCTION: Renal events are common in cancer patients and malignancy is a prevalent complication in both patients transplanted and under kidney replacement therapy (KRT). In recent years, onco-nephrology has been developed as a subspecialty whose scope has not been well established yet. The aim of our study was to assess resident and senior physicians' knowledge and expectations about onco-nephrology. METHODS AND MATERIALS: Two anonymous self-administered online questionnaires were developed by a multidisciplinary team and distributed to French residents and senior physicians. RESULTS: Two hundred twenty-eight physicians answered the survey, including 128 (56%) nephrologists, of which 98 (43%) were senior physicians and 130 (57%) were residents. Nephrologists rated their confidence in their ability to face onco-nephrological situation at 6/10 (interquartile range (IQR) 4.0-7.0) and oncologists at 6.0/10 (5.0-7.0). Managing cancer drugs in patients on KRT or in transplanted patients and discussion about introducing dialysis in cancer patients were designated as the most challenging topics. Asking if they had received appropriate learning, residents' median agreement was ranked at 3.0/10 (2.0-4.0). Forty-six percent of the respondents considered available resources as not appropriate. Specialized onco-nephrology consultations were accessible for 21% of the respondents. Finally, respondents thought there is a strong need for a national working group (8.3/10) with 87% of them expecting new reliable guidelines. CONCLUSION: The present survey revealed physicians' expectations about onco-nephrology implementation in France. An appropriate answer could be the creation of a national working group. Therefore, GRIFON (Groupe de Recherche Interdisciplinaire en OncoNéphrologie) has recently been created.

Inclusion of patients with chronic kidney disease in randomized phase 3 clinical trials in patients with prostate, breast, lung, and colorectal cancer.

The objective of this study was to determine the proportion of phase 3 clinical trials investigating a systemic therapy for patients with prostate, breast, lung, or colorectal cancer that excluded patients with Chronic Kidney Disease (CKD) and the exclusion criteria chosen, if any. A search was conducted using the ClinicalTrials.gov database to identify eligible studies. Of the 268 included trials, 185 (69%) had at least one renal exclusion criteria. Of these 185 trials, 116 (63%) had an undefined exclusion criterion. Only disease site was associated with exclusion of patients with CKD in the univariate analysis, but no factors in the multivariate analysis. There are several potential barriers to including patients with CKD in clinical trials. Nevertheless, solutions can be proposed to allow the inclusion of these patients. This would allow them to access to innovative therapeutic strategies, but also allow a better applicability of trial results to this patient population.

Discussion on methadone initiation protocols: A case report.

Through a concrete case, we discuss the main published protocols to initiate methadone and illustrate the advantages and disadvantages of rapid or gradual initiation and on-demand or fixed doses with rescue doses. Daily doses can vary widely depending on the protocol chosen. An on-demand administration could lead to an overdose as illustrated in our case. A better understanding of particularities and limitations of these protocols could lead to safer methadone initiation. Systematic comparison of different protocols and calculation of the daily dose should be a standard in clinical practice.

[Targeted therapies and high blood pressure]. / Thérapies ciblées et hypertension artérielle.

"Targeted therapies and hypertension The recent advent of molecular targeted agents represents an important improvement in the management of cancer patients. The administration of therapies targeting the vascular endothelial growth factor or its receptor could be associated with side effects including cardiovascular complications (hypertension, heart Failure, QT interval prolongation). Hypertension due to molecular targeted agents is considered as a class effect, which can affect nearly 90% of treated patients; its management is most often based on the introduction of anti-hypertensive treatment and more rarely on dose drug reduction."

"Thérapies ciblées et hypertension artérielle La mise à disposition des thérapies ciblées et notamment des thérapies moléculaires ciblées antiangiogéniques constitue une avancée importante dans la prise en charge des patients atteints de cancers. L'administration des thérapies ciblées ciblant le vascular endothelial growth factor ou son récepteur peut s'accompagner d'effets indésirables, dont des complications cardiovasculaires (hypertension artérielle, insuffisance cardiaque, allongement de l'intervalle QT). L'hypertension secondaire à l'administration des thérapies ciblées est un effet de classe, pouvant affecter près de 90 % des patients traités ; sa prise en charge repose le plus souvent sur l'introduction d'un traitement antihypertenseur et plus rarement sur la modulation de la posologie de la thérapie ciblée."