[Change in the prevention of kidney stones]. / Lithiase rénale, un changement de paradigme?

Kidney stone is one of the most frequent disorders of the urinary tract. Once the stone has passed, the management should be oriented on prevention. If changes in lifestyle and diet should be implemented in a true therapeutic education of the patient, prescription of drugs has been recently challenged by the NOSTONE trial. This randomized controlled trial did not show any benefit of hydrochlorothiazide in the prevention of recurrence of kidney stone event in patients with calcium-containing stone. Therefore, prescription of thiazide in the sole purpose of decreasing kidney stone recurrence should be limited and the risk/benefit of this treatment should be carefully balanced for each case.

La maladie rénale lithiasique est une des affections les plus fréquentes de l'axe urinaire. Une fois l'expulsion du calcul obtenue, la prise en charge est orientée sur la prévention. Si les modifications diététiques et comportementales doivent être implémentées dans le cadre d'une véritable éducation thérapeutique, la prescription de traitements médicamenteux préventifs est remise en question par l'étude NOSTONE. Cette étude randomisée contrôlée n'a pas montré de bénéfice de l'hydrochlorothiazide dans la prévention de la récidive des calculs à contenu calcique. Dès lors, la prescription de thiazide en monothérapie dans le but de diminuer les récidives de calculs doit être limitée et le risque/bénéfice soigneusement évalué dans chaque cas.

[Granulomatosis with polyangiitis: what's new?] / Granulomatose avec polyangéite : quoi de neuf ?

Within the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (GPA) is the most frequent. The incidence is around 10 to 20 cases/million/year. Clinical manifestations are varied, with ENT, lungs and kidneys most frequently involved. ANCA are pathogenic by triggering neutrophil activation, which leads to vascular damage. Detection of ANCA is most helpful in establishing the diagnosis, but serology may be negative in GPA limited to the airways. Diagnostic work-up and therapy require a multidisciplinary approach. Treatment includes an induction and maintenance phase, combining corticosteroids and immunosuppressive drugs. It aims at limiting the risk of relapses, which is important in GPA, and at reducing corticosteroids toxicity.

La granulomatose avec polyangéite (GPA) fait partie des vasculites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA). La maladie touche principalement la sphère ORL, les poumons et les reins. Son incidence est de 10 à 20 cas/million/année. Les ANCA sont pathogéniques en induisant une activation des polynucléaires neutrophiles, entraînant des lésions endothéliales. Le diagnostic est facilité par la détection des ANCA, qui peuvent cependant être absents dans les formes ORL limitées. La prise en charge est multidisciplinaire. Le traitement comprend une phase d'induction et une autre de maintien de la rémission, associant corticostéroïdes et immunosuppresseurs. L'objectif du traitement est de limiter le risque important de rechute et de réduire la toxicité des corticostéroïdes.

[Anti-glomerular basement membrane disease]. / Maladie des anticorps anti-membrane basale glomérulaire.

Anti-glomerular basement membrane disease is a rare disease. In its classical presentation it associates rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage, linked to the presence of antibodies targeting type IV collagen in the glomerular and alveolar basal membrane. Anti-GBM disease warrants prompt medical management to limit permanent kidney damage and mortality. Treatment includes plasma exchanges to quickly remove pathogenic antibodies and immunosuppressants to stop their production. This article reviews the pathogenesis and current treatments.

La maladie des anticorps anti-membrane basale glomérulaire (anti-MBG) est une entité rare. Dans sa présentation classique, elle associe une glomérulonéphrite rapidement progressive et une hémorragie alvéolaire diffuse liée à des anticorps dirigés contre le collagène de type IV des membranes basales glomérulaire et alvéolaire. Les pronostics rénal et vital sont engagés. Le traitement doit être prompt et comprend des plasmaphérèses visant à éliminer les anticorps pathogéniques ainsi qu'une immunosuppression destinée à supprimer leur production. Cet article passe en revue la pathogénie et les traitements actuels.

[Nephrotic syndrome and other high-level proteinuria]. / Syndrome néphrotique de l'adulte et autres protéinuries de fort debit.

High level albuminuria and the nephrotic syndrome are pathognomonic of glomerular renal disease and must be distinguished from other high-level proteinuria. Causes of the nephrotic syndrome are numerous and its clinical significance requires diagnostic rigor to propose targeted treatment and prevent possible complications and renal functional decline. A nephrotic syndrome can also be an early expression of potentially severe non-renal medical conditions. It should be considered in any patient with edema, regardless of age and comorbidities.

L'albuminurie de fort débit et le syndrome néphrotique sont pathognomoniques d'une atteinte rénale glomérulaire et doivent être distingués des autres protéinuries de fort débit. Les causes du syndrome néphrotique sont nombreuses et sa signification clinique impose une rigueur diagnostique afin de proposer un traitement ciblé et de prévenir d'éventuelles complications et un déclin fonctionnel rénal. Un syndrome néphrotique peut être aussi l'expression plus ou moins précoce d'affections médicales non rénales éventuellement sévères et évolutives. Il faut donc y penser chez tout patient qui présente des œdèmes, quels que soient son âge et ses comorbidités.

A stone in the bone.

Primary hyperoxaluria (PH) is a group of diseases due to mutations in genes coding for enzymes involved in oxalate metabolism. Three types of PH are identified depending on the gene mutated. Type 1 is the most frequent with 80% of the cases, while PH2 and PH3 are rarer. The severity of renal involvement varies between the three types. Indeed, between 60% and 80% of PH1 but only 20% of PH2 patients will reach end-stage kidney disease. In PH3 patients, dialysis is uncommon. Because oxalate clearance is impaired in CKD patients, oxalate can precipitate in various organs leading to systemic oxalosis. We report an uncommon presentation of bone oxalosis associated with hypercalcemia in a dialyzed patient. This report emphasizes the difficulties to diagnose primary hyperoxaluria and the challenge of treating dialyzed patients.

Exposure to alirocumab during the first trimester of pregnancy: A case report.

BACKGROUND: Familial hypercholesterolemia can be efficiently treated with combined lipid-lowering drugs. Lipid-lowering drugs are usually withdrawn for pregnancy and breastfeeding, ideally preconception, followed by lipid apheresis, however, careful plans can be precipitated due to unexpected pregnancy. CASE: A 28-year old woman with familial hypercholesterolemia due to heterozygous LDLR mutations had an LDL-cholesterol level at 14.6 mmol/L and Lp(a) at 1150 mg/L. She required a three-vessel coronary artery bypass graft, drug-eluting stents, rosuvastatin, ezetimibe, and alirocumab at maximal dosage. Contraception was advised during the following 12 months, with a planned drug withdrawal to bridge with lipid apheresis, such as the direct adsorption of lipoproteins (DALI). However, an unplanned pregnancy required an abrupt stop of all oral medications at six gestational weeks, except for aspirin. Lipid apheresis controlled LDL-cholesterol in the range of 4.9-7.9 mmol/L (before DALI session) to 1.2-3.2 mmol/L (after DALI session). Later, the regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum later confirmed by magnetic resonance imaging. CONCLUSIONS: A causal link between the early pregnancy exposure to PCSK9 inhibitors (or statins and ezetimibe taken concomitantly) and the observed complete agenesis of the corpus callosum seems unlikely in this case. Guidelines do not specifically recommend preconception measures to lower fetal and/or maternal risks of patients with severe FH considering pregnancy. We argue that lipid apheresis and other measures should be discussed with women with FH and maternity project on an individual basis, until pharmacoepidemiology studies assessing the safety of PCSK9 inhibitors in pregnancy are available.

Spectrum of Kidney Involvement in Patients with Myelodysplastic Syndromes.

INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by a high prevalence of associated autoimmune manifestations. Kidney involvement has been rarely reported in MDS patients. We report on the spectrum of kidney pathological findings in MDS patients. METHODS: We retrospectively identified MDS patients who had undergone a kidney biopsy between 2001 and 2019 in nine Swiss and French nephrology centres. RESULTS: Nineteen patients (median age 74 years [63-83]) were included. At the time of kidney biopsy, eleven (58%) patients had extra-renal auto-immune manifestations and sixteen (84%) presented with acute kidney injury. Median serum creatinine at diagnosis was 2.8 mg/dL [0.6-8.3] and median urinary protein to creatinine ratio was 1.2 g/g [0.2-11]. Acute tubulo-interstitial nephritis (TIN) was present in seven (37%) patients. Immunofluorescence study in one patient with acute TIN disclosed intense IgG deposits along the tubular basement membrane and Bowman's capsule. Other kidney pathological features included ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis (n = 3), membranous nephropathy (n = 2), IgA nephropathy (n = 1), IgA vasculitis (n = 1), immunoglobulin-associated membrano-proliferative glomerulonephritis type I (n=1), crescentic C3 glomerulopathy (n = 1), fibrillary glomerulonephritis (n = 1) and minimal change disease (n = 1). Eleven (58%) patients received immunosuppressive treatments, among whom one developed a severe infectious complication. After a median follow-up of 7 month [1-96], nine (47%) patients had chronic kidney disease stage 3 (n = 6) or 4 (n = 3) and five (26%) progressed to end-stage kidney disease. Three patients died. CONCLUSIONS: MDS are associated to several autoimmune kidney manifestations, predominantly acute TIN. MDS are to be listed among the potential causes of autoimmune TIN.

Water-Soluble Vitamin Levels and Supplementation in Chronic Online Hemodiafiltration Patients.

INTRODUCTION: Supplementation of water-soluble vitamins is a common practice in hemodialysis patients, but dosages are largely based on conventional hemodialysis techniques. The aim of this study was to assess the status of water-soluble vitamins in patients on hemodiafiltration (HDF), and attempt to determine optimal dose of vitamin supplements. METHODS: This monocentric study included 40 patients on thrice-weekly chronic HDF. At baseline, all patients received 2 tablets of Dialvit containing B and C vitamins after each dialysis session. Predialysis samples of B and C vitamins were measured in both blood (n = 40) and a subgroup of dialysate (n = 6) samples. A second blood sample was obtained in 24 patients 3 months after dose adjustment of the vitamin supplement. RESULTS: At baseline, B-vitamin levels were high with, respectively, 0.4%, 10.0%, and 89.6% of patients in the low, normal, and high reference range. For vitamin C, most patients were in the normal range (5.0%, 82.5%, and 12.5% in low, normal, and high reference range). Three months after dose reduction, B vitamin levels decreased but stayed mostly at or above the normal range (1.4%, 25.7%, 72.9% in low, normal, and high reference range). Three patients (12.5%) developed vitamin C deficiency on low-dose substititon. CONCLUSION: This study shows that the levels of most vitamins are above the normal range in patients on HDF receiving a classic dose of vitamin supplements, vitamin C excepted. Our study suggests that the classic dose of postdialysis vitamin B supplements may be reduced.

[Rhabdomyolysis: early management]. / Rhabdomyolyse: prise en charge médicale initiale.

Rhabdomyolysis is defined by myalgia, potentially painful myoedema and muscular weakness due to death of muscular fiber in the striated muscle. Frequent etiologies include physical effort, intoxication (alcohol, drugs and medication) and physical trauma. Depletion of myocyte' s adenosine triphosate (ATP) leads to an increase in intracellular calcium and myocyte death. Diagnosis relies on creatine kinase (CK) levels. The clinical spectrum of rhabdomyolysis includes an asymptomatic increased amount of CK as well as severe, life threatening complications such as acute renal failure and electrolyte disorders. Treatment is based on prevention and addressing complications.

La rhabdomyolyse, définie comme étant les conséquences de la destruction du muscle strié, se caractérise par l'association de myalgies, d'un myo-œdème éventuellement douloureux et d'une faiblesse musculaire. Parmi les étiologies fréquentes, on peut citer l'effort, les causes toxiques (alcool et médicament) et traumatiques. Elle résulte d'un épuisement de l'adénosine triphosphate du myocyte, menant à une augmentation du calcium intracellulaire et à sa destruction. Le diagnostic repose sur le dosage de la créatine kinase (CK). Le spectre de la rhabdomyolyse englobe une élévation asymptomatique des CK, mais aussi des complications redoutables telles qu'une insuffisance rénale aiguë sévère ou des troubles électrolytiques pouvant mettre en jeu le pronostic vital. Le traitement est centré sur la prévention et la prise en charge de ces complications.

Prevalence and Description of Hyponatremia in a Swiss Tertiary Care Hospital: An Observational Retrospective Study.

Background: Hyponatremia (serum sodium concentration <135 mEq/L) is the most common electrolyte abnormality among hospitalized patients. Our aim was to study the epidemiology of hyponatremia in hospitalized patients, as well as the short-term mortality rates, the length of stay (LOS), and associated hospital costs. Methods: This retrospective cohort study included 6,539 hospitalizations in the internal medicine ward of a Swiss tertiary-care teaching hospital between January 1, 2012, and December 31, 2018 (42.7% women, mean age 69 years). Using serum sodium concentration, we identified hospitalizations with hyponatremia and calculated the prevalence of overall hyponatremia, admission hyponatremia (AH), hospital-acquired hyponatremia (HAH), and persistent hyponatremia (PH) at discharge. We also studied the impact of hyponatremia on 30-day readmissions, in-hospital and 30-day mortality, and hospital LOS and costs, using multivariable logistic regression and Cox proportional hazards models, with normal natremia as reference. Results: Prevalence of overall hyponatremia was 32.5% [95% confidence interval (CI), 31.3-33.6%], while prevalence of PH among hospitalizations with AH and HAH was 33.7% (31.7-35.8%). After multivariable adjustment, hyponatremia was associated with increased hospital costs (CHF 19,025 ± 485 vs. 14,962 ± 341, p < 0.001) and LOS (13.4 ± 0.2 vs. 10.7 ± 0.2 days, p < 0.001). Increased severity of hyponatremia was associated with higher hospital costs and LOS (p for trend <0.001). There was a trend toward more frequent 30-day readmissions associated with hyponatremia [adjusted odds ratio (OR), 1.15 (1.01-1.31), p = 0.032], mainly with PH: adjusted OR = 1.41 (1.17-1.71), p < 0.001. No association was found between severity of hyponatremia and readmissions. Hyponatremia was associated with an increase of in-hospital [adjusted OR = 1.94 (1.49-2.53), p < 0.001] and 30-day mortality: adjusted OR = 1.80 (1.44-2.24), p < 0.001. Increased severity of hyponatremia was associated with higher in-hospital and 30-day mortality (p for trend < 0.001). Conclusions: Hyponatremia is highly prevalent among hospitalized patients and associated with an increase of LOS, early hospital readmission, in-hospital and 30-day mortality, and hospital costs. PH was associated with a substantial increase of the risk of early hospital readmission and 30-day mortality.

Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group.

Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill defined. This report, by an international multidisciplinary working group of obstetricians, nephrologists, hematologists, intensivists, neonatologists, and complement biologists, summarizes the current knowledge of these potentially severe disorders and proposes a practical clinical approach to diagnose and manage an episode of pregnancy-associated TMA. This approach takes into account the timing of TMA in pregnancy or postpartum, coexisting symptoms, first-line laboratory workup, and probability-based assessment of possible causes of pregnancy-associated TMA. Its aims are: to rule thrombotic thrombocytopenic purpura (TTP) in or out, with urgency, using ADAMTS13 activity testing; to consider alternative disorders with features of TMA (preeclampsia/eclampsia; hemolysis elevated liver enzymes low platelets syndrome; antiphospholipid syndrome); or, ultimately, to diagnose complement-mediated atypical hemolytic uremic syndrome (aHUS; a diagnosis of exclusion). Although they are rare, diagnosing TTP and aHUS associated with pregnancy, and postpartum, is paramount as both require urgent specific treatment.

[COVID-19 from the nephrologist's point of view]. / Vue sur le COVID-19 depuis la néphrologie.

During the actual pandemic of COVID-19, it has become clear that the virus causing this devastating disease, SARS-CoV2, targets not only the lungs but also other organs. In this article, we discuss the known or suspected interactions between the virus and the kidneys, as well as their clinical presentations. We also discuss how the pandemic has altered the activities of nephrologists and the logistics of a Swiss dialysis center.

Au cours de la pandémie de COVID-19, nombre de spécialistes se questionnent sur les interactions du virus avec différents tissus et organes au-delà de l'atteinte pulmonaire. Pour diverses raisons, l'effervescence a aussi gagné le néphrologue. Ce bref article présente les différents aspects de l'interaction virus-rein, l'impact de la pandémie sur les activités néphrologiques et tente de répondre à quelques questions d'actualité.

[The management of hypertriglyceridemia and the risk of pancreatitis]. / Prise en charge des hypertriglycéridémies et du risque de pancréatite.

In the face of hypertriglyceridemia, the potential causes must be assessed to choose the best medical therapeutic option. In cases of secondary hypertriglyceridemia, physicians should use treatments targeting the pathophysiological mechanisms underlying the lipid disorder. Lifestyle interventions are the cornerstone of an effective treatment, to achieve controlled glycemia, blood pressure and weight loss. Only in cases where these measures are insufficient, fibrates can be trialed although their clinical benefit is controversial, with special caution when combined with statins (risk of rhabdomyolysis). Plasmapheresis or intravenous insulin therapy are only used in severe situations after a multidisciplinary decision process in the hospital setting. The clinical case presented here reminds us to assess hypertriglyceridemia in the face of any acute pancreatitis.

Les causes d'une hypertriglycéridémie doivent être explorées pour choisir la meilleure approche thérapeutique. En cas d'hypertriglycéridémie secondaire, il est préférable de cibler le mécanisme physiopathologique du désordre lipidique. Les mesures hygiéno-diététiques restent la clé de voûte du traitement, pour atteindre un bon contrôle glycémique, tensionnel et pondéral. Uniquement en cas d'échec, les fibrates peuvent être évoqués bien que leur bénéfice clinique soit controversé, avec une attention particulière en cas de bithérapie par statine et fibrate (risque de rhabdomyolyse). La plasmaphérèse ou l'insulinothérapie intraveineuse sont réservées aux situations sévères et décidées avec les différents spécialistes en milieu hospitalier. Le cas clinique présenté ici est un rappel que l'hypertriglycéridémie devrait être recherchée devant toute pancréatite aiguë.

[Immune checkpoint inhibitors and renal toxicity†: update about an emerging pathology]. / Inhibiteurs de points de contrôle immunitaires et atteinte rénale†: mise au point sur une pathologie émergente.

Recently, comprehension of immune mechanisms involved in anti-tumor responses has permitted the development of new oncologic drugs called immune checkpoint inhibitors. These drugs act by restoring anti-tumor responses. With their increasing use, we note a rise in the incidence rate of immune related adverse events, which can affect many organs. Renal toxicity, more precisely tubulointerstitial nephritis, is still not well understood but an emerging complication.

Récemment, la compréhension des mécanismes immuns impliqués dans la réponse antitumorale a permis de développer de nouveaux traitements oncologiques, les inhibiteurs de points de contrôle immunitaires. L'action de ceux-ci repose sur une rupture des mécanismes de tolérance immune envers la tumeur. Avec leur développement, on observe l'apparition d'effets indésirables d'un nouveau genre, s'apparentant à une autoimmunité et touchant différents systèmes. La toxicité rénale, sous la forme d'une néphrite tubulo-interstitielle, est une complication encore méconnue mais émergeante.